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The Pan African Medical Journal 2022
Topics: Humans; Microphthalmos; Siblings; Anophthalmos
PubMed: 36523275
DOI: 10.11604/pamj.2022.43.69.35059 -
BMJ Case Reports Aug 2021
Topics: Anophthalmos; Female; Humans; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 34404668
DOI: 10.1136/bcr-2021-244684 -
Scientific Reports Jul 2021The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown....
The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance.
Topics: Anophthalmos; Bacteria; Conjunctiva; DNA, Ribosomal; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Merkel Cells; Merkel cell polyomavirus; Middle Aged; Torque teno virus
PubMed: 34321490
DOI: 10.1038/s41598-021-92642-w -
Korean Journal of Ophthalmology : KJO Feb 2021We sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A...
PURPOSE
We sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A comparison with prostheses produced using manual manufacturing methods was then performed.
METHODS
To confirm the biological and physiochemical safety, cytotoxicity, systemic acute toxicity, intradermal reaction, and skin sensitization tests were conducted according to the International Organization for Standardization guidelines. The compressive strength of the prostheses was also tested. Further, a case series of three patients who wore the 3D printed prostheses for more than eight hours daily for 4 weeks was executed. Self-assessments by these individuals using a questionnaire and safety evaluations focusing on the occurrence of conjunctival inflammation or allergic reactions according to the Cornea and Contact Lens Research Unit criteria by slit-lamp examination and similarity assessment were completed.
RESULTS
The 3D printed ocular prostheses met the necessary qualifications per the biological and physiochemical safety tests, showing the absence of cytotoxicity, acute systemic toxicity, intradermal reactivity, and skin-sensitizing potency. Also, there was no difference in strength test results between previous ocular prostheses and the 3D printed ones. Self-assessment by the patients yielded satisfactory results, with no significant difference in the level of satisfaction reported for the 3D printed and previous handmade ocular prostheses. The 3D printed prosthesis did not trigger any side effects in the conjunctival sac and showed similar objective findings with respect to the color of the iris, sclera, and vessel patterns.
CONCLUSIONS
Our study confirms the biologic and physiochemical safety of 3D-printed ocular prostheses created using computer-aided design technology and a sublimation technique. The patients' questionnaires and the judgment of the ophthalmologists/ocularists showed that the 3D printed ocular prosthesis was acceptable in function and appearance through a case series report.
Topics: Computer-Aided Design; Eye, Artificial; Humans; Printing, Three-Dimensional; Prosthesis Design; Prosthesis Implantation
PubMed: 33307623
DOI: 10.3341/kjo.2020.0125 -
Journal of Medical Genetics Jul 2019A single variant in (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify...
BACKGROUND
A single variant in (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.
METHODS
Three families, including 15 affected individuals with syndromic X-linked microphthalmia, underwent analyses including linkage analysis, exome sequencing and targeted gene sequencing. The consequences of two identified variants in were evaluated using quantitative PCR and RNAseq.
RESULTS
Genetic linkage analysis in family 1 supported a candidate region on Xq27-q28, which included . Exome sequencing identified a hemizygous polyadenylation signal (PAS) variant, chrX:153,195,397T>C, c.*43A>G, which segregated with the disease. Targeted sequencing of affected males from families 2 and 3 identified distinct PAS variants, chrX:g.153,195,401T>C, c.*39A>G and chrX:g.153,195,400T>C, c.*40A>G. All three variants were absent from gnomAD. Quantitative PCR and RNAseq showed reduced mRNA levels and abnormal 3' UTRs in affected individuals. Targeted sequencing of in 376 additional affected individuals failed to identify variants in the PAS.
CONCLUSION
These data show that PAS variants are the most common variant type in -associated syndromic microphthalmia, suggesting reduced RNA is the molecular mechanism by which these alterations cause microphthalmia/anophthalmia. We reviewed recognised variants in PAS associated with Mendelian disorders and identified only 23 others, indicating that harbours more than 10% of all known PAS variants. We hypothesise that PAS in other genes harbour unrecognised pathogenic variants associated with Mendelian disorders. The systematic interrogation of PAS could improve genetic testing yields.
Topics: 3' Untranslated Regions; Alleles; Anophthalmos; Female; Genes, X-Linked; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Lod Score; Male; Microphthalmos; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E; Pedigree; Poly A; Sequence Analysis, DNA; X Chromosome Inactivation
PubMed: 30842225
DOI: 10.1136/jmedgenet-2018-105836 -
Medicina (Kaunas, Lithuania) Jun 2021Prolonged hyperinsulinemic hypoglycemia in infancy can result in developmental sequelae. A mutation in the paired box-6 gene () has been reported to cause disorders in...
Prolonged hyperinsulinemic hypoglycemia in infancy can result in developmental sequelae. A mutation in the paired box-6 gene () has been reported to cause disorders in oculogenesis and neurogenesis. A limited number of cases of diabetes mellitus in adults with a mutation suggest that the gene also plays a role in glucose homeostasis. The present case report describes a boy with a mutation, born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. This patient provides novel evidence that connects to glucose homeostasis and highlights that life-threatening hypoglycemia or early onset glucose intolerance may be encountered. The role of in glucose metabolism and insulin regulation should be further investigated.
Topics: Anophthalmos; Humans; Hypoglycemia; Infant; Male; Mutation; PAX6 Transcription Factor; Pedigree
PubMed: 34200146
DOI: 10.3390/medicina57060582 -
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 -
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