-
Clinical & Experimental Optometry Jan 2013The aim was to develop tools to measure the condition of ocular prostheses and the socket's response to prosthetic eyewear. (Comparative Study)
Comparative Study
BACKGROUND
The aim was to develop tools to measure the condition of ocular prostheses and the socket's response to prosthetic eyewear.
METHODS
A novel staining technique for displaying deposits on prosthetic eyes was developed. Equal interval perceptual grading scales for measuring inferior palpebral conjunctival inflammation, and anterior and posterior stained surface deposits on prosthetic eyes were developed from 800 photographs of 43 volunteers. The photographs for each scale were chosen by the authors. A group of four ophthalmologists, three optometrists and three senior students was consulted about selection criteria and asked to position the photographs along a 1.5 m rule to determine equal intervals. Photographs judged not to represent exactly equal perceptual intervals were exchanged with others from the original pool. The final scales (a five-photograph scale for inflammation and two 11 photograph scales for deposits) were assessed for inter-rater reliability and test-retest reliability by groups of senior optometry students.
RESULTS
Standard deviations for inter-rater reliability tests were 0.52 scale units for the inflammation scale, 0.99 for the anterior surface deposits scale and 1.03 for the posterior surface deposits scale. The standard deviation of the test-retest differences for inflammation was 0.6 scale units and for both anterior and posterior surface deposits it was 0.71.
CONCLUSIONS
A novel technique for displaying and measuring the intensity and extent of deposit formation on prosthetic eye surfaces has been described. The two equal interval perceptual grading scales that have been developed to quantify the extent of deposit formation together with the equal interval perceptual scale for grading severity of palpebral conjunctival inflammation will for the first time allow the effects of prosthetic eye wear to be evaluated. Further research to validate the scale for palpebral conjunctival inflammation in a clinical setting is recommended. The technique for staining deposits on prosthetic eyes is recommended for clinical practice.
Topics: Anophthalmos; Biomedical Research; Eye, Artificial; Humans; Ophthalmology; Optometry; Prosthesis Design; Reproducibility of Results
PubMed: 22672062
DOI: 10.1111/j.1444-0938.2012.00754.x -
Molecular Vision 2011To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia.
PURPOSE
To further explore the spectrum of mutations in the Visual System Homeobox 2 (VSX2/CHX10) gene previously found to be associated with autosomal recessive microphthalmia.
METHODS
We screened 95 probands with syndromic or isolated developmental ocular conditions (including 55 with anophthalmia/microphthalmia) for mutations in VSX2.
RESULTS
Homozygous mutations in VSX2 were identified in two out of five consanguineous families with isolated microphthalmia. A novel missense mutation, c.668G>C (p.G223A), was identified in a large Pakistani family with multiple sibships affected with bilateral microphthalmia. This p.G223A mutation affects the conserved CVC motif that was shown to be important for DNA binding and repression activities of VSX2. The second mutation, c.249delG (p.Leu84SerfsX57), was identified in an Iranian family with microphthalmia; this mutation has been previously reported and is predicted to generate a severely truncated mutant protein completely lacking the VSX2 homeodomain, CVC domain and COOH-terminal regions.
CONCLUSIONS
Mutations in VSX2 represent an important cause of autosomal recessive microphthalmia in consanguineous pedigrees. Identification of a second missense mutation in the CVC motif emphasizes the importance of this region for normal VSX2 function.
Topics: Amino Acid Sequence; Animals; Anophthalmos; Asian People; Base Sequence; Case-Control Studies; Child; Consanguinity; Conserved Sequence; DNA Mutational Analysis; Female; Genes, Recessive; Homeodomain Proteins; Homozygote; Humans; Male; Mice; Microphthalmos; Molecular Sequence Data; Mutation; Pedigree; Retina; Sequence Alignment; Transcription Factors; Zebrafish
PubMed: 21976963
DOI: No ID Found -
American Journal of Medical Genetics.... Jan 2022SOX2 variants and deletions are a common cause of anophthalmia and microphthalmia (A/M). This article presents data from a cohort of patients with SOX2 variants, some of...
SOX2 variants and deletions are a common cause of anophthalmia and microphthalmia (A/M). This article presents data from a cohort of patients with SOX2 variants, some of whom have been followed for 20+ years. Medical records from patients enrolled in the A/M Research Registry and carrying SOX2 variants were reviewed. Thirty-seven patients were identified, ranging in age from infant to 30 years old. Eye anomalies were bilateral in 30 patients (81.1%), unilateral in 5 (13.5%), and absent in 2 (5.4%). Intellectual disability was present in all with data available and ranged from mild to profound. Seizures were noted in 18 of 27 (66.6%) patients, usually with abnormal brain MRIs (10/15, 66.7%). Growth issues were reported in 14 of 21 patients (66.7%) and 14 of 19 (73.7%) had gonadotropin deficiency. Genitourinary anomalies were seen in 15 of 19 (78.9%) male patients and 5 of 15 (33.3%) female patients. Patients with SOX2 nucleotide variants, whole gene deletions or translocations are typically affected with bilateral or unilateral microphthalmia and anophthalmia. Other associated features include intellectual disability, seizures, brain anomalies, growth hormone deficiency, gonadotropin deficiency, and genitourinary anomalies. Recommendations for newly diagnosed patients with SOX2 variants include eye exams, MRI of the brain and orbits, endocrine and neurology examinations. Since the clinical spectrum associated with SOX2 alleles has expanded beyond the originally reported phenotypes, we propose a broader term, SOX2-associated disorder, for this condition.
Topics: Anophthalmos; DNA; Female; Humans; Male; Microphthalmos; Registries; SOXB1 Transcription Factors
PubMed: 34562068
DOI: 10.1002/ajmg.a.62518 -
Arquivos Brasileiros de Oftalmologia 2020To identify problems caused by prosthesis-socket volume imbalances in anophthalmic sockets; and to evaluate rehabilitation with dermofat graft as a solution.
PURPOSES
To identify problems caused by prosthesis-socket volume imbalances in anophthalmic sockets; and to evaluate rehabilitation with dermofat graft as a solution.
METHODS
We retrospectively reviewed medical records of patients operated in our clinic (between May 2011 and June 2016) with dermofat grafts to treat anophthalmic socket-related problems. During the preoperative examinations, ophthalmologists recorded the presence of eyelid problems due to the socket volume deficit, upper and lower fornix deficiency, deepening in the upper eyelid sulcus, epiphora and secretion, lower eyelid laxity, ptosis, entropion, and ectropion. Following the surgical repair, new prosthesis suitable for the resulting socket area were implemented for all the patients. The mean follow-up period was 27.42±16 months (ranging from 10-62 months). On the last control examinations, ophthalmologists recorded solved and unsolved socket problems that were present preoperatively.
RESULTS
We included 16 men and 5 women in this study. The mean age was 38.3 ± 18.4 years (range, 5-75 years). The mean duration of preoperative prosthesis use was 9.4 ± 6.8 years (range, 1-30 years). Preoperatively, 7 patients had only orbital volume deficits, and 14 had socket volume displacements in addition to the volume deficits. After the dermofat graft implantations, the remaining deficits were corrected during another surgical session: 6 patients underwent ptosis corrections, 5 lateral canthal suspensions, 5 lower fornix with mucosal graft formations, and 2 upper fornix formations with mucosal grafts. All patients were able to use prosthesis postoperatively.
CONCLUSION
The use of dermofat grafts to correct anophthalmic socket problems caused by orbital volume deficits or volume displacements is an effective, reliable, and reproducible surgical method.
Topics: Adolescent; Adult; Aged; Anophthalmos; Child; Child, Preschool; Eyelids; Female; Humans; Male; Middle Aged; Ophthalmologic Surgical Procedures; Orbit; Orbital Implants; Plastic Surgery Procedures; Retrospective Studies; Young Adult
PubMed: 31531549
DOI: 10.5935/0004-2749.20200003 -
Developmental Medicine and Child... Jun 2001This study aimed to describe clinical findings, pedigrees, and possible environmental risk factors in children with clinical anophthalmos and remnant microphthalmos in...
This study aimed to describe clinical findings, pedigrees, and possible environmental risk factors in children with clinical anophthalmos and remnant microphthalmos in either eye in southern India. Twenty-four children (14 male, 10 female; mean age 10.3 years, age range 1.3 to 18 years,) were recruited from schools for the blind, hospitals, and community-based rehabilitation programmes in Andhra Pradesh, India, over 1 year. Family members were examined, and mothers interviewed. Fifteen children had anophthalmos and nine had remnant microphthalmos in one or both eyes. Twelve children had associated systemic findings, of which six were major and six were minor abnormalities. Information on consanguinity was available in 19 children, 12 of whom had consanguineous parents. Five children had a positive family history. Two mothers had a history of night blindness, and one had a history of pesticide exposure during pregnancy. High rates of consanguinity suggest a genetic recessive aetiology.
Topics: Adolescent; Anophthalmos; Child; Child, Preschool; Consanguinity; Female; Genes, Recessive; Humans; India; Infant; Male; Pedigree; Phenotype; Pregnancy; Risk Factors; Surveys and Questionnaires; Visual Acuity
PubMed: 11409828
DOI: 10.1017/s0012162201000731 -
Yonsei Medical Journal Apr 2005This report presents a rare example of a bilateral congenital anophthalmos and an agenesis of the optic pathways. The MR imaging studies revealed that the eyeballs,...
This report presents a rare example of a bilateral congenital anophthalmos and an agenesis of the optic pathways. The MR imaging studies revealed that the eyeballs, optic nerves, optic chiasm, optic tracts and optic radiation were absent. The chromosomal examination was normal. Mild mental retardation was also observed. Apart from the rarity of the anophthalmos and the total absence of the optic pathways, no etiologic reason for this pathology could be detected, which makes this case more significant.
Topics: Abnormalities, Multiple; Adult; Anophthalmos; Female; Humans; Intellectual Disability; Magnetic Resonance Imaging; Optic Chiasm; Optic Nerve; Visual Pathways
PubMed: 15861506
DOI: 10.3349/ymj.2005.46.2.296 -
Developmental Biology Mar 2007Sox2, which encodes an SRY-like HMG box transcription factor, is critical for vertebrate development. Sox2 mediates its transcriptional effects through the formation of...
Sox2, which encodes an SRY-like HMG box transcription factor, is critical for vertebrate development. Sox2 mediates its transcriptional effects through the formation of complexes with specific co-factors, many of which are unknown. In this report, we identify Oct-1, encoded by the Pou2f1 gene, as a co-factor for Sox2 in the context of mouse lens and nasal placode induction. Oct-1, Sox2, and Pax6 are co-expressed during lens and nasal placode induction and during subsequent developmental stages. Genetic combination of Sox2 and Pou2f1 mutant alleles results in impaired induction of the lens placode, an ocular phenotype that includes anophthalmia, and a complete failure of nasal placode induction. These ocular and nasal phenotypes closely resemble those observed in Pax6 null embryos. Moreover, we identify DNA-binding sites that support the cooperative formation of a complex between Sox2 and Oct-1 and mediate Sox2/Oct-1-dependent transactivation of the Pax6 lens ectoderm enhancer in vitro. We demonstrate that the same Sox- and Octamer-binding sites are essential for Pax6 enhancer activity in the lens placode and its derivatives in transgenic mouse embryos. Collectively, these results indicate that Pou2f1, Sox2 and Pax6 are interdependent components of a molecular pathway utilized in both lens and nasal placode induction.
Topics: Animals; Anophthalmos; Base Sequence; Binding Sites; Cell Line; DNA Primers; DNA-Binding Proteins; Eye Proteins; Gene Expression Regulation, Developmental; Homeodomain Proteins; Lens, Crystalline; Mice; Mice, Inbred C3H; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Nasal Mucosa; Nose; Octamer Transcription Factor-1; PAX6 Transcription Factor; Paired Box Transcription Factors; Phenotype; Rabbits; Repressor Proteins; SOXB1 Transcription Factors; Trans-Activators; Transcriptional Activation
PubMed: 17140559
DOI: 10.1016/j.ydbio.2006.10.047 -
NeuroImage. Clinical 2020Anophthalmia, characterized by the absence of an eye(s), is a rare major birth defect with a relatively unexplored neuroanatomy. Longitudinal comparison of white matter...
Anophthalmia, characterized by the absence of an eye(s), is a rare major birth defect with a relatively unexplored neuroanatomy. Longitudinal comparison of white matter development in an anophthalmic (AC) very preterm (VPT) child with both binocular VPT and full-term (FT) children provides unique insights into early neurodevelopment of the visual system. VPT-born neonates (<32wks gestational age), including the infant with unilateral anophthalmia, underwent neuroimaging every two years from birth until 8 years. DTI images (N = 168) of the optic radiation (OR) and a control track, the posterior limb of the internal capsule (PLIC), were analysed. The diameter of the optic nerves (ON) were analysed using T1-weighted images. Significant group differences in FA and AD were found bilaterally in the OR and PLIC. This extends the literature on altered white matter development in VPT children, being the first longitudinal study showing stable group differences across the 4, 6 and 8 year timepoints. AC showed greater deficits in FA and AD bilaterally, but recovered towards VPT group means from 4 to 8 years-of-age. Complete lack of binocular input would be responsible for these early deficits; compensatory mechanisms may facilitate structural improvement over time. AC's ON exhibited significant atrophy ipsilateral to the anophthalmic eye. Functionally, AC displayed normal visual acuity and form perception, but naso-temporal bias in motion perception. Following these groups and AC longitudinally enabled novel understanding of the joint influence of monocular vision and VPT birth on neurodevelopment.
Topics: Anophthalmos; Brain; Child; Child, Preschool; Diffusion Tensor Imaging; Female; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Longitudinal Studies; Male; White Matter
PubMed: 32798909
DOI: 10.1016/j.nicl.2020.102373 -
International Journal of Molecular... Apr 2023Vision is likely our most prominent sense and a correct development of the eye is at its basis. Early eye development is tightly connected to the development of the...
Vision is likely our most prominent sense and a correct development of the eye is at its basis. Early eye development is tightly connected to the development of the forebrain. A single eye field and the prospective telencephalon are situated within the anterior neural plate (ANP). During normal development, both domains are split and consecutively, two optic vesicles and two telencephalic lobes emerge. If this process is hampered, the domains remain condensed at the midline. The resulting developmental disorder is termed holoprosencephaly (HPE). The typical ocular finding associated with intense forms of HPE is cyclopia. However, also anophthalmia and coloboma can be associated with HPE. Here, we report that a correct balance of Bone morphogenetic proteins (BMPs) and their antagonists are important for forebrain and eye field cleavage. Experimental induction of a BMP ligand results in a severe form of HPE showing anophthalmia. We identified a dysmorphic forebrain containing retinal progenitors, which we termed crypt-oculoid. Optic vesicle evagination is impaired due to a loss of and, consecutively, of . Our data further suggest that the subduction of prospective hypothalamic cells during neurulation and neural keel formation is affected by the induction of a BMP ligand.
Topics: Animals; Anophthalmos; Bone Morphogenetic Proteins; Gene Expression Regulation, Developmental; Holoprosencephaly; Ligands; Prospective Studies; Transcription Factors; Zebrafish
PubMed: 37175759
DOI: 10.3390/ijms24098052 -
American Journal of Human Genetics Jan 2011Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We...
Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.
Topics: Animals; Base Sequence; Chromosome Mapping; Chromosomes, Human, Pair 14; Codon, Nonsense; Extremities; Eye; Genes, Recessive; Genetic Loci; Humans; Limb Deformities, Congenital; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Microphthalmos; Molecular Sequence Data; Optic Nerve; Osteonectin; RNA Splicing; Waardenburg Syndrome
PubMed: 21194678
DOI: 10.1016/j.ajhg.2010.11.012