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Reproductive Toxicology (Elmsford, N.Y.) Jan 2020Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the...
Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.
Topics: Animals; Embryonic Development; Female; Gene Expression Regulation, Developmental; Melanins; Mice, Inbred C57BL; Organ Size; Radiation Injuries, Experimental; Retinal Pigment Epithelium; X-Rays
PubMed: 31705956
DOI: 10.1016/j.reprotox.2019.10.002 -
Molecular Vision 2012To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural...
PURPOSE
To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural fold homeobox gene (RAX) in anophthalmia and associated cerebral malformations.
METHODS
Three patients with clinical anophthalmia and first-degree relatives from two consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurologic examination, and blood tests. Cerebral magnetic resonance imaging (MRI) was performed in the index cases of both families. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of RAX was performed after PCR amplification.
RESULTS
Clinical bilateral anophthalmia was observed in all three patients. General and neurologic examinations were normal; obesity and delay in psychomotor development were observed in the isolated case. Orbital MRI showed a hypoplastic orbit with present but rudimentary extraocular muscles and normal lacrimal glands. Cerebral MRI showed agenesis of the optic nerves, optic tracts, and optic chiasma. In the index case of family A, the absence of the frontal and sphenoidal sinuses was also noted. In the index case of family B, only the sphenoidal sinus was absent, and there was significant cortical atrophy. The three patients carried a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. Parents were healthy heterozygous carriers. No mutations were detected in orthodenticle homeobox 2 (OTX2), ventral anterior homeobox 1 (VAX1), or sex determining region Y-box 2 (SOX2).
CONCLUSIONS
This is the first report of a homozygous splicing RAX mutation associated with autosomal recessive bilateral anophthalmia. To our knowledge, only two isolated cases of anophthalmia, three null and one missense case affecting nuclear localization or the DNA-binding homeodomain, have been found to be caused by compound heterozygote RAX mutations. A novel missense RAX mutation was identified in three patients with bilateral anophthalmia and a distinct systemic and neurologic phenotype. The mutation potentially affects splicing of the last exon and is thought to result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized.
Topics: Anophthalmos; Base Sequence; Cerebral Cortex; Child; Consanguinity; Egypt; Exons; Eye Proteins; Female; Genes, Recessive; Homeodomain Proteins; Homozygote; Humans; Introns; Male; Molecular Sequence Data; Mutation, Missense; Orbit; Otx Transcription Factors; Pedigree; Retina; SOXB1 Transcription Factors; Transcription Factors
PubMed: 22736936
DOI: No ID Found -
Indian Journal of Ophthalmology Sep 2021We describe an objective method to measure the volume of a dermis-fat graft (DFG) implant for socket reconstruction. We reviewed the charts of 10 patients undergoing...
We describe an objective method to measure the volume of a dermis-fat graft (DFG) implant for socket reconstruction. We reviewed the charts of 10 patients undergoing dermis fat grafting as a primary or secondary implant for anophthalmic socket reconstruction between January 2018 and December 2019. The amount of the DFG required to replace the volume of an appropriate spherical implant for the operated eye was predetermined. The volume of the DFG implant was measured by the water displacement method as per the Archimedes principle. Patient demographics, complications, and the outcome were analyzed regarding cosmesis and volume replacement. All patients were satisfied with the final cosmesis. Follow-up ranged from 6 to 18 months (mean 10.7 months). Thus, we concluded that the water displacement method is a simple and easy procedure to objectively determine the amount of the autologous DFG needed to replace the volume in an anophthalmic socket.
Topics: Anophthalmos; Dermis; Eye, Artificial; Humans; Orbit; Orbital Implants
PubMed: 34427258
DOI: 10.4103/ijo.IJO_130_21 -
Acta Ophthalmologica Nov 2020To evaluate health-related quality of life (HR-QoL), vision-related (VR-)QoL and perceptual visual dysfunction (PVD) among individuals with anophthalmia (A) and...
PURPOSE
To evaluate health-related quality of life (HR-QoL), vision-related (VR-)QoL and perceptual visual dysfunction (PVD) among individuals with anophthalmia (A) and microphthalmia (M) treated with ocular prosthesis.
METHODS
The study comprised 15 individuals (mean age 6.6 years; range 1.7-14.1) with unilateral A or M. Three validated instruments measuring HR-QoL and VR-QoL were used: The Pediatric QoL Inventory (PedsQL), consisting of physical and psychosocial self-report and parent-proxy report (2-18 years); Children's Visual Function Questionnaire (CVFQ); and Effects of Youngsters' Eyesight on Quality of Life (EYE-Q). Perceptual visual dysfunctions (PVDs) were assessed by history taking according to a specific protocol.
RESULTS
A/M children and their parents showed low HR-QoL scores (PedsQL total score: 66.3; 69.6) compared with controls (83.0; 87.61) (p = 0.0035 and <0.0001, respectively, unpaired t-test). No differences were found between A/M children and parents, but parents tended to underestimate their children's emotional state. A/M children with subnormal visual acuity (VA) for age scored lower in physical health compared with A/M children with normal VA (p = 0.03, Mann-Whitney U-test). No significant VR-QoL differences between A/M children and references or between A/M children with subnormal or normal VA for age were found. More A/M children than controls exhibited PVDs in ≥1 area (7/11 versus 4/118; p < 0.0001, Fisher's exact test).
CONCLUSION
A/M individuals show poor HR-QoL and increased PVDs. No difference in QoL was found between children and parents, though the children tended to score lower in emotional well-being. A/M children with subnormal VA showed lower physical health score. These problems indicate the necessity of a thorough multidisciplinary assessment and follow-up of children with A/M.
Topics: Adolescent; Anophthalmos; Child; Child, Preschool; Eye, Artificial; Female; Follow-Up Studies; Humans; Infant; Male; Microphthalmos; Quality of Life; Retrospective Studies; Surveys and Questionnaires; Visual Acuity
PubMed: 32356375
DOI: 10.1111/aos.14424 -
Child's Nervous System : ChNS :... Aug 2021Lenz microphthalmia syndrome (LMS) is an allelic X-linked syndrome correlated to a null mutation of B cell lymphoma (BCL-6) corepressor (BCOR) gene, which is essential... (Review)
Review
Lenz microphthalmia syndrome (LMS) is an allelic X-linked syndrome correlated to a null mutation of B cell lymphoma (BCL-6) corepressor (BCOR) gene, which is essential in the early embryonic development. Phenotypically, this rare hereditary syndrome is characterized by microphthalmia/anophthalmia and other eye disorders; mental disability; dental, ear, and digital abnormalities; and variable malformations affecting the heart, skeleton (limbs and/or spine), and genitourinary tract. In this paper, a case of a young adult with LMS affected additionally by immuno-hematological disturbances was treated with decompressive craniectomy after domestic accidental fall. Case description and a brief review of the current literature about this rare condition are presented here.
Topics: Abnormalities, Multiple; Anophthalmos; Female; Humans; Intellectual Disability; Microphthalmos; Pregnancy; Young Adult
PubMed: 33491151
DOI: 10.1007/s00381-020-05035-1 -
Graefe's Archive For Clinical and... Mar 2023To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of...
PURPOSE
To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS).
METHODS
In this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated.
RESULTS
Patients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004).
CONCLUSIONS
Measuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.
Topics: Humans; Matrix Metalloproteinase 9; Prospective Studies; Point-of-Care Systems; Dry Eye Syndromes; Tears; Conjunctivitis; Immunoassay; Anophthalmos; Osmolar Concentration; Biomarkers; Inflammation
PubMed: 36357674
DOI: 10.1007/s00417-022-05895-0 -
European Journal of Human Genetics :... Oct 2023Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can...
Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can display variable neurodevelopmental features, but the relationship to the ALDH1A3 variants remains unclear. Here, we describe seven unrelated families with biallelic pathogenic ALDH1A3 variants: four compound heterozygous and three homozygous. All affected individuals had bilateral anophthalmia/microphthalmia (A/M), three with additional intellectual or developmental delay, one with autism and seizures and three with facial dysmorphic features. This study confirms that individuals with biallelic pathogenic ALDH1A3 variants consistently manifest A/M, but additionally display neurodevelopmental features with significant intra- and interfamilial variability. Furthermore, we describe the first case with cataract and highlight the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M.
Topics: Humans; Microphthalmos; Anophthalmos; Mutation; Aldehyde Oxidoreductases; Eye Abnormalities; Phenotype
PubMed: 36997679
DOI: 10.1038/s41431-023-01342-8 -
Canadian Medical Association Journal Mar 1919
PubMed: 20311239
DOI: No ID Found -
The British Journal of Ophthalmology Nov 1949
Topics: Anophthalmos; Eye; Humans
PubMed: 15392449
DOI: 10.1136/bjo.33.11.685 -
Eye (London, England) Dec 2021To evaluate morphological alterations of meibomian glands (MGs) in the dry anophthalmic socket syndrome (DASS).
PURPOSE
To evaluate morphological alterations of meibomian glands (MGs) in the dry anophthalmic socket syndrome (DASS).
METHODS
Fifteen unilateral anophthalmic patients wearing cryolite glass prosthetic eyes were enrolled. All patients with clinical blepharitis or other significant eyelid abnormalities were excluded. In vivo laser scanning confocal microscopy (LSCM) of the MGs in the lower eyelids both on the anophthalmic side and the healthy fellow eye was performed to quantify acinar unit density, acinar unit diameter, acinar unit area, meibum secretion reflectivity, the inhomogeneous appearance of the glandular interstice, and inhomogeneous appearance of the acinar walls.
RESULTS
The lower eyelids of the anophthalmic sockets revealed a significant reduction of the acinar unit density (p = 0.003) as well as a significantly more inhomogeneous appearance of the periglandular interstices (p = 0.018) and the acinar unit walls (p = 0.015) than the healthy fellow eyelid. However, there were no significant differences regarding the acinar unit diameter, acinar unit area, and meibum secretion reflectivity of the MGs on the anophthalmic side compared to the healthy fellow eyelid (p ≥ 0.05, respectively).
CONCLUSIONS
The eyelids of anophthalmic sockets without clinical blepharitis demonstrate a reduced density of MG acinar units and a more inhomogeneous appearance of the periglandular interstices and the acinar unit walls. This can cause meibomian gland dysfunction contributing to DASS and suggests early treatment of these symptomatic patients, even in the clinical absence of any blepharitis signs.
Topics: Anophthalmos; Blepharitis; Eyelid Diseases; Humans; Meibomian Glands; Microscopy, Confocal; Syndrome; Tears
PubMed: 33564141
DOI: 10.1038/s41433-021-01426-z