-
European Journal of Ophthalmology Jul 2021Insufficient orbital volume in an anophthalmic socket is a major problem for the placement of an ocular prosthesis. This study reports the outcomes of the use of...
INTRODUCTION
Insufficient orbital volume in an anophthalmic socket is a major problem for the placement of an ocular prosthesis. This study reports the outcomes of the use of autologous pericranium graft in association with a large primary or secondary orbital implant in patients with a contracted socket and large orbital volume deficit.
METHODS
This was a retrospective single-institution study. Participants were 13 patients with contracted socket, volume deficit, and insufficient conjunctiva to cover the new implant divided into two groups, A ( = 3) and B ( = 10), according to the baseline condition of the socket. Surgery was primary evisceration (group A only) and placement of a large orbital implant followed by an autologous pericranium graft over the implant (groups A and B).
RESULTS
Mean follow-up duration for the patient series was 9.5 months (range 9-24). Complete epithelialization of the pericranium graft was recorded at 47.3 days of follow-up (range 33-67). No cases of implant exposure or shrinkage were noted during follow-up. Main postoperative complications were conjunctival granuloma (five patients, 38.5%), conjunctival seroma (one patient, 7.7%). All patients were satisfied with the aesthetic outcome.
CONCLUSION
Autologous pericranial graft was effective in reconstructing the contracted socket so that the anophthalmic socket could accommodate a larger or secondary orbital implant. The efficacy of this procedure needs to be confirmed in a larger patient series.
Topics: Anophthalmos; Autografts; Eye Enucleation; Eye Evisceration; Humans; Orbital Implants; Postoperative Complications; Prosthesis Implantation; Retrospective Studies
PubMed: 32615826
DOI: 10.1177/1120672120940597 -
American Journal of Medical Genetics.... Aug 2022Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or...
Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.
Topics: Anophthalmos; Exome; Humans; Infant; Microphthalmos; Mutation, Missense; Exome Sequencing
PubMed: 35716026
DOI: 10.1002/ajmg.a.62874 -
The British Journal of Ophthalmology Nov 2023Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant...
BACKGROUND/AIMS
Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant proportion of childhood blindness worldwide. Clear understanding of MAC aetiology and comorbidities is essential to providing patients with appropriate care. However, current management is unstandardised and molecular diagnostic rates remain low, particularly in those with unilateral presentation. To further understanding of clinical and genetic management of patients with MAC, we charted their real-world experience to ascertain optimal management pathways and yield from molecular analysis.
METHODS
A prospective cohort study of consecutive patients with MAC referred to the ocular genetics service at Moorfields Eye Hospital between 2017-2020.
RESULTS
Clinical analysis of 50 MAC patients (15 microphthalmia; 2 anophthalmia; 11 coloboma; and 22 mixed) from 44 unrelated families found 44% had additional ocular features (complex) and 34% had systemic involvement, most frequently intellectual/developmental delay (8/17). Molecular analysis of 39 families using targeted gene panels, whole genome sequencing and microarray comparative genomic hybridisation identified genetic causes in, 28% including novel variants in six known MAC genes (, , , , and ), and a molecular diagnostic rate of 33% for both bilateral and unilateral cohorts. New phenotypic associations were found for (bilateral sensorineural hearing loss) and (unilateral microphthalmia).
CONCLUSION
This study highlights the importance of thorough clinical and molecular phenotyping of MAC patients to provide appropriate multidisciplinary care. Routine genetic testing for both unilateral and bilateral cases in the clinic may increase diagnostic rates in the future, helping elucidate genotype-phenotype correlations and informing genetic counselling.
Topics: Humans; Anophthalmos; Microphthalmos; Coloboma; Prospective Studies; Eye Abnormalities; Eye Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 36192130
DOI: 10.1136/bjo-2022-321991 -
Boletin Medico Del Hospital Infantil de... 2020Transient pigmentary lines of the newborn are uncommon cutaneous lesions of unknown etiology. To date, only a few cases have been described.
BACKGROUND
Transient pigmentary lines of the newborn are uncommon cutaneous lesions of unknown etiology. To date, only a few cases have been described.
CASE REPORT
A patient with a combination of transient pigmentary lines and ocular malformation is described. Molecular analysis of the SRY-box 2 (SOX2) and MIFT genes was conducted to rule out any monogenetic etiology.
CONCLUSIONS
Worldwide, this is the eighth case of transient pigmentary lines of the newborn reported, and the first associated with anophthalmia. No mutations in the analyzed genes (SOX2 and MIFT) were identified. Therefore, somatic mutations could be responsible for this anomaly.
Topics: Anophthalmos; Humans; Hyperpigmentation; Infant, Newborn; Mutation
PubMed: 32496470
DOI: 10.24875/BMHIM.19000191 -
Frontiers in Behavioral Neuroscience 2020Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these...
Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.
PubMed: 33488367
DOI: 10.3389/fnbeh.2020.609660 -
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 -
Genes Oct 2022Anophthalmia (missing eye) describes a failure of early embryonic ocular development. Mutations in a relatively small set of genes account for 75% of bilateral...
Anophthalmia (missing eye) describes a failure of early embryonic ocular development. Mutations in a relatively small set of genes account for 75% of bilateral anophthalmia cases, yet 25% of families currently are left without a molecular diagnosis. Here, we report our experimental work that aimed to uncover the developmental and genetic basis of the anophthalmia characterising the X-linked (eye-ear reduction) X-ray-induced allele in mouse that was first identified in 1947. Histological analysis of the embryonic phenotype showed failure of normal eye development after the optic vesicle stage with particularly severe malformation of the ventral retina. Linkage analysis mapped this mutation to a ~6 Mb region on the X chromosome. Short- and long-read whole-genome sequencing (WGS) of affected and unaffected male littermates confirmed the linkage but identified no plausible causative variants or structural rearrangements. These analyses did reduce the critical candidate interval and revealed evidence of multiple variants within the ancestral DNA, although none were found that altered coding sequences or that were unique to . To investigate early embryonic events at a genetic level, we then generated mouse ES cells derived from male embryos and wild type littermates. RNA-seq and accessible chromatin sequencing (ATAC-seq) data generated from cultured optic vesicle organoids did not reveal any large differences in gene expression or accessibility of putative cis-regulatory elements between and wild type. However, an unbiased TF-footprinting analysis of accessible chromatin regions did provide evidence of a genome-wide reduction in binding of transcription factors associated with ventral eye development in , and evidence of an increase in binding of the Zic-family of transcription factors, including Zic3, which is located within the -refined critical interval. We conclude that the refined critical region at chrX: 56,145,000-58,385,000 contains multiple genetic variants that may be linked to altered regulation but does not contain a convincing causative mutation. Changes in the binding of key transcription factors to chromatin causing altered gene expression during development, possibly through a subtle mis-regulation of Zic3, presents a plausible cause for the anophthalmia phenotype observed in , but further work is required to determine the precise causative allele and its genetic mechanism.
Topics: Mice; Male; Animals; Anophthalmos; Regulatory Sequences, Nucleic Acid; Transcription Factors; Chromatin; DNA; Homeodomain Proteins
PubMed: 36292683
DOI: 10.3390/genes13101797 -
European Journal of Human Genetics :... Mar 2023ARHGAP35 has known roles in cell migration, invasion and division, neuronal morphogenesis, and gene/mRNA regulation; prior studies indicate a role in cancer in humans...
ARHGAP35 has known roles in cell migration, invasion and division, neuronal morphogenesis, and gene/mRNA regulation; prior studies indicate a role in cancer in humans and in the developing eyes, neural tissue, and renal structures in mice. We identified damaging variants in ARHGAP35 in five individuals from four families affected with anophthalmia, microphthalmia, coloboma and/or anterior segment dysgenesis disorders, together with variable non-ocular phenotypes in some families including renal, neurological, or cardiac anomalies. Three variants affected the extreme C-terminus of the protein, with two resulting in a frameshift and C-terminal extension and the other a missense change in the Rho-GAP domain; the fourth (nonsense) variant affected the middle of the gene and is the only allele predicted to undergo nonsense-mediated decay. This study implicates ARHGAP35 in human developmental eye phenotypes. C-terminal clustering of the identified alleles indicates a possible common mechanism for ocular disease but requires further studies.
Topics: Humans; Animals; Mice; Eye Abnormalities; Microphthalmos; Anophthalmos; Coloboma; Phenotype; Mutation; Repressor Proteins; Guanine Nucleotide Exchange Factors
PubMed: 36450800
DOI: 10.1038/s41431-022-01246-z -
The Pan African Medical Journal 2022
Topics: Humans; Microphthalmos; Siblings; Anophthalmos
PubMed: 36523275
DOI: 10.11604/pamj.2022.43.69.35059 -
Neuroscience and Biobehavioral Reviews Dec 2019Investigating the changes in the brain that result from a loss of sensory input has provided significant insight into the considerable capacity of the brain to... (Review)
Review
Investigating the changes in the brain that result from a loss of sensory input has provided significant insight into the considerable capacity of the brain to reorganise. One of the difficulties in studying sensory-deprived populations is that the time and extent of sensory loss vary significantly. In this review, we consider the changes in the human brain associated with complete absence of visual input resulting from bilateral congenital anophthalmia, in which the eyes fail to develop. We describe the functional reorganisation and associated structural and connectivity changes that occur in the brain of those affected by the condition. By considering animal models of this condition, we investigate the changes that may be occurring on a scale that is not captured by human in vivo imaging techniques. Finally, we lay out a model pathway for taking auditory information to the occipital cortex that may be specific to anophthalmia.
Topics: Anophthalmos; Auditory Perception; Blindness; Brain; Humans; Magnetic Resonance Imaging; Neuroimaging; Neuronal Plasticity
PubMed: 31626815
DOI: 10.1016/j.neubiorev.2019.10.006