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Children (Basel, Switzerland) Dec 2022Congenital clinical anophthalmos and blind microphthalmos describe the absence of an eye or the presence of a small eye in the orbit. Between 1999 and 2013, 97 children...
Congenital clinical anophthalmos and blind microphthalmos describe the absence of an eye or the presence of a small eye in the orbit. Between 1999 and 2013, 97 children with anophthalmos or microphthalmos were treated with self-inflating, hydrophilic gel expanders at the Rostock Eye Clinic. More than a decade later, this study investigated the perspective of patients and parents regarding the treatment, the surgical outcome, and the emotional and social well-being of the patients. A total of 22 families with 16 patients sighted in the other eye and six patients blind in both eyes participated. Questionnaires were developed, including items on physical, emotional, social, and medical aspects. The patients felt emotionally stable and integrated into their social environment, with no major limitations reported by the majority. These statements were confirmed by most of the parents. Parents (67%) indicated that the success of the operation was already apparent after the first intervention and that the current situation did not play a role in the patients' social environment. The study provided new insights into the therapy results, the postoperative care, and the social and emotional stability of the prosthesis-wearing patients, indicating the chosen expander methods as promising in terms of positive postoperative care.
PubMed: 36670585
DOI: 10.3390/children10010034 -
Human Genetics Sep 2019Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected,... (Review)
Review
Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected, cataractous eyes are easily to detect without major technical equipment. In mice, actually 145 genes or loci are known for anophthalmia, 269 for microphthalmia, and 180 for cataracts. Approximately, 25% of the loci are not yet characterized; however, some of the ancient lines are extinct and not available for future research. The phenotypes of the mutants represent a continuous spectrum either in anophthalmia and microphthalmia, or in microphthalmia and cataracts. On the other side, mouse models are still missing for some genes, which have been identified in human families to be causative for anophthalmia, microphthalmia, or cataracts. Finally, the mouse offers the possibility to genetically test the roles of modifiers and the role of SNPs; these aspects open new avenues for ophthalmogenetics in the mouse.
Topics: Animals; Anophthalmos; Cataract; Eye; Humans; Mice; Microphthalmos; Mutation; Phenotype
PubMed: 30919050
DOI: 10.1007/s00439-019-01995-w -
Phenomics (Cham, Switzerland) Aug 2022Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying...
Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families, we screened 425 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the two probands of two three-generation Chinese families diagnosed with microphthalmos. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation. We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, Peroxidasin () c.3165C>T (p.Pro1055Pro) and c.2640C>G (p.Arg880Arg), were found in Family 1, and Crystallin Beta B2 () c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the p.Gly161Arg mutation was a deleterious effect mutation. In conclusion, the three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early pre-symptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.
PubMed: 36939803
DOI: 10.1007/s43657-022-00053-2 -
Clinical Genetics May 2020Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We...
Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF, TMEM98, MFRP, and PRSS56. Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.
Topics: Australia; Cohort Studies; Eye; Eye Diseases, Hereditary; Female; Frameshift Mutation; Glaucoma, Angle-Closure; Humans; Hyperopia; Male; Membrane Proteins; Microphthalmos; Pedigree; Serine Proteases; Transcription Factors
PubMed: 32052405
DOI: 10.1111/cge.13722 -
Biology Open Jun 2023As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of...
As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes' altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.
Topics: Animals; Fibronectins; Leucine; Membrane Glycoproteins; Microphthalmos; Zebrafish
PubMed: 37259881
DOI: 10.1242/bio.059784 -
Acta Ophthalmologica Dec 2020Congenital anophthalmia (A) and microphthalmia (M) are rare developmental defects, which could be isolated or syndromic. Our objective was to describe a cohort of...
PURPOSE
Congenital anophthalmia (A) and microphthalmia (M) are rare developmental defects, which could be isolated or syndromic. Our objective was to describe a cohort of children and young adults with A/M treated with ocular prosthesis, emphasizing clinical features, diagnosis, treatment, and follow-up.
METHODS
Eighteen individuals (10 female) with unilateral A (n = 3) and M (n = 15) with a mean age of 9.5 years (range 0.8-31.8) and treated with ocular prosthesis were included. Data on medical history, clinical examinations and management of ocular prosthesis were collected. Genetic screening with microarray and whole-exome sequencing targeting 121 A/M-related genes was performed.
RESULTS
A/M appeared isolated (seven cases) or as part of a syndromic condition (11 cases). In 4/16 patients, mutations were detected in TFAP2A, CHD7, FOXE3 and BCOR-genes. In one patient, a possibly causal microdeletion 10q11 was shown. Associated ocular anomalies such as cataract and cysts were found in 16 (89%) of the A/M eyes, and in nine (50%) ophthalmological findings were found in the fellow eyes. The median ages at which the conformer and ocular prosthesis first were initiated were 7.8 months and 1.5 years. 16/17 patients fulfilled satisfactory orbital growth and cosmetic results when treated with ocular prosthesis from an early age.
CONCLUSION
Based upon our findings, a multidisciplinary approach, including genetic assessment, is necessary to cover all aspects of A/M. Imaging, ultrasound and visual evoked potentials should be included. Early management is crucial for the outcome, in terms of non-ocular findings, vision in the fellow eye, and for facial cosmetic development.
Topics: Adolescent; Adult; Anophthalmos; Child; Child, Preschool; Disease Management; Female; Humans; Infant; Male; Microphthalmos; Phenotype; Prognosis; Young Adult
PubMed: 32436650
DOI: 10.1111/aos.14427 -
Scientific Reports Mar 2022Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been... (Observational Study)
Observational Study
Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been published pertaining to the clinical manifestations and management of this condition; however, few reports have reported detailed histopathological findings, which are the focus of this study, in addition to highlighting the basic demographics in these cases. This was a retrospective, observational study of all consecutive enucleated microphthalmic globes (with or without cysts) at 2 tertiary eye hospitals in Riyadh, Saudi Arabia. Globes were classified into 2 groups: severe microphthalmos (axial length or mean diameter less than 10 mm in infancy or 12 mm after age 1 year) and mild microphthalmos based on larger measurements. Clinical and demographic data collected included sex, age at enucleation, eye involvement, nationality/region, consanguinity, family history of eye anomaly, pregnancy, systemic disease, or syndromes. For histopathological data, a descriptive analysis was mostly performed. For correlations of some of our qualitative data, Fisher's exact test was used. Eleven cases (6 mild and 5 severe microphthalmos) were initially identified with a female to male ratio of 4:7. Ten patients were Saudis, 7 of whom were from the central region. Consanguinity was found in 36% (4/11), and 3 of them had other ocular or systemic abnormalities (duodenal atresia, microcephaly, kidney agenesis, cryptophthalmos, and dysmorphic facial features). Histopathological data were available for 10 cases, half of which showed a coloboma and/or anterior segment anomaly. There was no significant correlation among gender, severity of microphthalmos or the presence of coloboma, although severe microphthalmic globes had a higher median of abnormal intraocular structures (9-interquartile range = 2 compared to 6-interquartile range = 1 in the mild group). Aphakia was found in half of the globes with associated anterior segment dysgenesis. We have concluded that microphthalmos is a visually disabling congenital anomaly that can be isolated or associated with other periocular or systemic anomalies, possibly in relation to consanguinity in our cases. Congenital aphakia was found in half of these cases and was mostly associated with absent Descemet's membrane and agenesis of anterior chamber angle structures, supporting previously suggested embryological concepts. These findings necessitate further wider genetic testing and proper premarital counseling in Saudi Arabia.
Topics: Coloboma; Demography; Eye Abnormalities; Female; Humans; Infant; Male; Microphthalmos; Retrospective Studies
PubMed: 35347187
DOI: 10.1038/s41598-022-09261-2 -
Journal of Ophthalmology 2021Nanophthalmos is a clinical phenotype of simple microphthalmos, in which the anterior and posterior segments of the eyeball do not develop into a normal size without... (Review)
Review
Nanophthalmos is a clinical phenotype of simple microphthalmos, in which the anterior and posterior segments of the eyeball do not develop into a normal size without other major ocular or systemic anomalies. Typical clinical manifestations of nanophthalmos include short axial length, thickened sclera, small cornea, shallow anterior chamber, and increased lens-to-eye volume ratio. Currently, there is a lack of recognized diagnostic criteria for nanophthalmos. With the development of eye examination technologies, such as biological measurement and imaging examination, visualization and quantification of the eyeball's shape and structure in nanophthalmos can be realized. New clinical features have been reported, which are of great significance for diagnosing and treating nanophthalmos. This review introduces the related concepts of nanophthalmos and the new developments in its clinical characterization.
PubMed: 33777447
DOI: 10.1155/2021/8853811 -
Journal of Ophthalmic & Vision Research 2023To report a case of a rare disease entity Posterior Microphthalmos Pigmentary Retinopathy Syndrome (PMPRS) in a 47-year-old female with a brief review of literature.
PURPOSE
To report a case of a rare disease entity Posterior Microphthalmos Pigmentary Retinopathy Syndrome (PMPRS) in a 47-year-old female with a brief review of literature.
CASE REPORT
A 47-year-old woman presented with a history of defective vision with an associated difficulty in night vision. Clinical workup was done, which included a thorough ocular examination showing diffuse pigmentary mottling of fundus, ocular biometry showing short axial length with normal anterior segment dimensions, electroretinography showing extinguished response, optical coherence tomography showing foveoschisis, and ultrasonography showing thickened sclera-choroidal complex. Findings were consistent with those reported by other authors with PMPRS.
CONCLUSION
Posterior microphthalmia with or without other ocular and systemic associations should be suspected in cases with high hyperopia. It is mandatory to carefully examine the patient at presentation and close follow-ups are needed to maintain visual function.
PubMed: 37181604
DOI: 10.18502/jovr.v18i2.13190 -
Saudi Journal of Ophthalmology :... 2019To report a critical case series of six patients with posterior microphthalmos (PM).
AIM
To report a critical case series of six patients with posterior microphthalmos (PM).
METHOD
Complete ophthalmologic examinations of all patients were performed using best-corrected visual acuity (BCVA), cycloplegic refraction, applanation tonometry, slit lamp biomicroscopy of the anterior segment, fundoscopy, A and B mode ultrasonography (USG), keratometry, and optic coherence tomography (OCT).
RESULTS
The most significant clinical characteristics of male patients aged 10-25 years was the presence of shorter posterior segments (mean: 15.27-18.91 mm) accompanying high hyperopia (mean +9.00 - +18.50 diopter) despite the normal anterior segment findings. The BCVA ranged between 20/320 and 40/100. Retinal folds were detected bilaterally on the papillomacular band in all patients. Although neurosensory retina was included in the fold in OCT images, retinal pigment epithelium, choroid, and sclera were not included in the fold. Pigmentary retinopathy was detected in one patient.
CONCLUSION
Despite normal anterior segment, posterior microphthalmos is characterized with high hyperopia, and shorter axial length and bilateral papillomacular retinal fold. Refractive amblyopia, uveal effusion syndrome, retinal detachment and macular hole are complications that can be corrected. Posterior microphthalmos must be kept in mind in patients with a normal anterior segment, and high hyperopia.
PubMed: 30930662
DOI: 10.1016/j.sjopt.2018.10.007