Assessment of Anxiety, Depression, Self-Esteem, and Quality-of-Life in Patients Undergoing Surgical Removal of an Eye.

Objectives: The objective of this study was to compare anxiety, depression, self-esteem, and quality of life in patients who underwent surgical removal of an eye with those of controls as well as to test the correlations of these variables in both groups. Methods: Beck anxiety inventory (BAI), Beck depression inventory (BDI), 36-item short-form health survey (SF-36), and Rosenberg self-esteem scale were administered to 29 patients with surgical removal of an eye and 30 control subjects. Results: The patient group had significantly lower scores on physical functioning, role limitations due to physical and emotional problems, pain, and general health perception domains of SF-36, as well as significantly higher BDI (p=0.004) scores as compared to controls. The study groups did not differ significantly with respect to BAI scores and energy/vitality, mental health, and social functioning domain scores of SF-36 (p>0.05). Conclusion: This population of monocular patients had similar mental health-related and Beck's Anxiety Inventory scores equivalent to the control group despite the surgical removal of one eye. However, lower scores for some SF-36 domains and higher depression levels in this patient group suggest that psychiatric rehabilitation should be considered after eye removal to improve the psychological outcomes and quality of life in these patients.

Trisomy 13 With Bilateral Congenital Anophthalmia: A Case Report.

Trisomy 13, also known as Patau syndrome, is a widely congenital anomaly syndrome characterized by microphthalmia, cleft lip, and palate, microcephaly with a sloping forehead, congenital heart disease, and polydactyly of the limbs. Patau syndrome is identified either prenatally or postnatally. Its survival rate is low, and most of the patients die even before their first year of life. The risk of trisomy 13 is higher in women of advanced maternal age. Brain and cardiovascular abnormalities are typically the primary factors contributing to the syndrome's poor prognosis. We report a case of a male newborn born at full term from a first-degree consanguineous marriage. Upon initial inspection, the patient had classic dysmorphic features, including low-set ears, a cleft lip and palate, a short neck, bilateral anophthalmia, and polydactyly of the limbs. After chromosomal analysis, the diagnosis was made, and a trisomy 13 was discovered.

Prevalence and prenatal diagnosis of congenital eye anomalies: A population-based study.

OBJECTIVE: To estimate the prevalence and trend of congenital eye anomalies (CEAs) and the rate of prenatal diagnosis over a 10-year period. DESIGN: Retrospective population-based registry study. SETTING: All maternity units in Paris, France, from 2010 to 2020. POPULATION: A cohort of 115 cases of CEA detected among all live births or stillbirths, after 22 weeks of gestation, and terminations of pregnancy. METHODS: The total prevalence of CEAs and prevalence of each specific CEA were calculated using 95% Poisson exact confidence intervals. MAIN OUTCOME MEASURES: The total prevalence of CEAs and the proportion of prenatal diagnosis of CEAs, and their evolution. RESULTS: The prevalence of CEAs was 4.1 (95% CI 3.4-5.0) cases, ranging between 3.1 and 5.7 cases, per 10 000 births. CEAs were prenatally diagnosed in 23.5% of cases. CEAs were bilateral in 51 cases (44.3%), unilateral in 43 cases (37.4%) and missing or unknown in 21 cases (18.3%). Of those with CEAs, 20.9% had genetic anomalies and 53.0% had at least one other extraocular anomaly. When detected prenatally, CEAs were bilateral in 15 cases (55.6%), unilateral in eight cases (29.6%) and missing in the four remaining cases. The prenatal diagnosis rate of CEAs associated with genetic anomalies, CEA cases with at least one other malformation and isolated CEA cases were 29.2%, 26.2% and 13.3%, respectively. CONCLUSIONS: In total, 115 cases of CEAs were observed during the study period, representing a total prevalence of 4.1 cases per 10 000 births. The overall prenatal detection rate of CEAs in our population was 23.5%, which dropped to 13.3% for isolated cases of CEAs.

Long term follow-up of axial length and orbital dimensions in congenital microphthalmia and anophthalmia.

PURPOSE: To evaluate axial length (AL), orbital width (OW) and height (OH) development in congenital microphthalmia and anophthalmia (MICA) using serial ultrasonography measurements. METHODS: A longitudinal prospective cohort (n = 74) of unilaterally and bilaterally affected MICA patients was followed from 2013 to 2022 at the university hospital in Amsterdam, the Netherlands. Clinical entity, age, severity category based on axial length, conformer treatment and intra-orbital cysts were registered. The main outcome measures were the absolute and relative growth of AL, OW and OH. Surgical and intra-orbital cyst cases were described separately. RESULTS: Absolute microphthalmic eye size increased in 27/49 (55%) unilateral MICA eyes, but growth arrest/decrease in the remaining could shift the case to a more severe category over time. A final affected/unaffected orbital symmetry ≥80% was seen in the large majority of unilateral cases (45/46 for OW, 43/46 for OH). Cases with AL < 10.5 mm had orbital symmetry <80% more often. Most orbital symmetry changes were seen in moderate and severe unilateral cases treated with 3D-printed conformer therapy starting at age <1 year, with 6/10 (60%) symmetry increase, 30% unchanged symmetry and 10% symmetry decrease. All cases older than 6.5 years (n = 6) did not show any change anymore, regardless of treatment. For bilateral and unilateral mild cases, orbital dimensions kept the same proportions during follow-up, with or without conformer treatment. CONCLUSIONS: Using severity categories in MICA based on relative AL may aid the decision to start conformer treatment, as most orbital symmetry changes were seen in moderate and severe unilateral cases receiving 3D-printed conformer therapy that started under age 1.

Stepwise self-inflating hydrogel expansion for congenital anophthalmia and blind microphthalmia: Over 15 years' experience in China.

BACKGROUND: Self-inflating hydrogel expanders have been used to treat anophthalmia and blind microphthalmia. This study aimed to investigate the long-term outcomes of treatment with self-inflating hydrogel expanders for congenital anophthalmia and blind microphthalmia. METHODS: In this retrospective study, the medical records of 161 patients with anophthalmia and blind microphthalmia who underwent hydrogel expansion were reviewed. We measured the palpebral fissure height (PFH), palpebral fissure length (PFL), and distance between the inner canthal and mid-nasal line (ICMN) before and after surgery. Cox regression analysis was conducted to determine which variables were related to the implantation of spherical expanders following hemispherical expander implantation. RESULTS: After treatment, the PFH and PFL increased significantly (p < 0.001). Complications including expander migration and extrusion occurred in 15 cases. Five patients needed enucleation or further dermis fat graft implantation because of insufficient expansion. The necessity for further spherical expansion was substantially related to a relative axial length (rAL) <0.5 (p = 0.007). CONCLUSION: Self-inflating hydrogel expansion can significantly increase the lid fissure. The occurrence of complications is rare, and surgical intervention can effectively address them. Abnormal eyes with a rAL of less than 0.5 demonstrate a higher possibility of needing additional orbital expansion.

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia. METHODS: In the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants. RESULTS: Clinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic. CONCLUSIONS: We have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

Associated anomalies in anophthalmia and microphthalmia.

Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.

Aplicación orbitaria de productos de relleno para optimización de simetría en pacientes con microftalmia o cavidades anoftálmicas adquiridas: revisión de la literatura / Aplicación orbitaria de productos de relleno para optimización de simetría en pacientes con microftalmia o cavidades anoftálmicas adquiridas: revisión de la literatura Orbital administration of fillers for optimization of symmetry in patients with microphthalmos or acquired anophthalmic sockets: A review

El tratamiento de la asimetría facial en pacientes con microftalmos o cavidades anoftálmicas adquiridas suele requerir cirugías reconstructivas agresivas. En los últimos años se han publicado trabajos sobre el uso de rellenos para optimizar la simetría del tejido orbitario, como técnicas mínimamente invasivas.Por este motivo, hemos realizado una revisión sistemática de la literatura publicada hasta el momento sobre la administración orbitaria de rellenos para el tratamiento de la pérdida de volumen. Se identificaron 14 artículos que cumplían con los criterios de selección; en los que se analizó el material utilizado, la técnica de inyección, el estudio anatómico de los pacientes antes del procedimiento y la presencia de complicaciones asociadas. Los materiales utilizados como relleno son: la grasa autóloga, la hidroxiapatita cálcica, el colágeno, el ácido hialurónico o el gel de poliacrilamida. Se aplicaron técnicas estándar de inyección peribulbar y retrobulbar, con escasas complicaciones asociadas, siendo la má grave el desarrollo de cuadros vaso-vagales. El seguimiento de los pacientes suele limitarse en la mayoría de los estudios a 12 meses, con variaciones significativas en la exoftalmometría posprocedimiento. En conclusión, la utilización de rellenos parece una práctica segura y con buenos resultados, aunque se precisan estudios con tiempo de seguimiento más prolongado que los publicados hasta el momento. (AU)

The treatment of facial asymmetry in patients with microphthalmos or acquired anophthalmic cavities usually requires aggressive reconstructive surgeries. In recent years, studies have been published on the use of fillers to optimize orbital tissue symmetry, as minimally invasive techniques.For this reason, we performed a systematic review of the literature published to date on the use of fillers for the treatment of volume loss in acquired anophthalmic or microphthalmic cavities. Fourteen articles were reviewed in which the material used, the injection technique, the anatomical study of the patients before the procedure and the presence of associated complications were analyzed.Various materials have been used as fillers, including autologous fat, calcium hydroxyapatite, collagen, hyaluronic acid, or polyacrylamide gel. Standard peribulbar and retrobulbar injection techniques were applied, with few associated complications, the most serious being the development of vasovagal symptoms. Patient follow-up is usually limited in most studies to 12 months.In Conclusion, the use of fillers seems to be a safe practice, with good results and few complications, although studies with longer follow-up times than those published to date would be required. (AU)

Orbital administration of fillers for optimization of symmetry in patients with microphthalmos or acquired anophthalmic sockets: A review.

The treatment of facial asymmetry in patients with microphthalmos or acquired anophthalmic sockets usually requires aggressive reconstructive surgeries. In recent years, studies have been published on the use of fillers to optimize orbital tissue symmetry, as minimally invasive techniques. For this reason, we performed a systematic review of the literature published to date on the use of fillers for the treatment of volume loss in acquired anophthalmic or microphthalmic cavities. Fourteen articles were reviewed in which the material used, the injection technique, the anatomical study of the patients before the procedure and the presence of associated complications were analyzed. Various materials have been used as fillers, including autologous fat, calcium hydroxyapatite, collagen, hyaluronic acid, or polyacrylamide gel. Standard peribulbar and retrobulbar injection techniques were applied, with few associated complications, the most serious being the development of vasovagal symptoms. Patient follow-up is usually limited in most studies to 12 months. In Conclusion, the use of fillers seems to be a safe practice, with good results and few complications, although studies with longer follow-up times than those published to date would be required.

Prenatal diagnosis of Sex determining region Y -box transcription factor 2 anophthalmia syndrome caused by germline mosaicism using next-generation sequencing: A case report.

Background: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene. Case Presentation: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents. Next-generation DNA sequencing was carried out to determine the family's possible cause of genetic mutation. Sanger sequencing was performed on the patients and their parents. Prenatal diagnosis was done in both pregnancies of the older brother's wife via chorionic villus sampling. A novel heterozygous pathogenic frameshift deletion variant (exon1:c.58_80del:p.G20fs) was identified in the SOX2 gene, which was confirmed by Sanger sequencing in both affected brothers and did not exist in healthy parents, indicating germline mosaicism. Conclusion: Most SOX2 mutations known look to arise de novo in probands and are diagnosed through anophthalmia or microphthalmia. Prenatal diagnosis should be offered to healthy parents with a child with SOX2 mutation every pregnancy.

Prevalence of anophthalmia etiological factors in patients treated in a reference center: A retrospective study.

Background: Ocular prosthesis rehabilitation has an important social, psychological, esthetic, and functional role. Congenital factors, trauma, and tumors, among others, can cause anophthalmia, and it is essential to identify the etiology to guide its prevention and treatment. Methods: The aim of this study was to retrospectively investigate the records of patients treated from 2013 to 2020 by the Oral and Maxillofacial Prosthesis Group, aiming to identify the prevalence of patients with anophthalmia and the etiology of their anophthalmia. After approval by the Human Research Ethics Committee, two calibrated researchers evaluated 520 records, identifying those from patients with anophthalmia. The inclusion criteria were records with complete and legible information from patients with anophthalmia and a description of their etiology. Descriptive statistics were performed, and etiological factors were categorized into trauma, congenital cause, end-stage eye disease, and tumor. Spearman's correlation was performed to verify the relation between gender and anophthalmia etiology, with a 5% significance level. Seventy-two records were included in the study. Results: It was observed that 33.4% of patients were women and 66.6% were men. The etiologies were physical trauma (52.4%), tumor (21.8%), end-stage eye disease (16.6%), and congenital cause (9.2%), and there was no correlation between gender and these etiologies (p = .301). Conclusion: Most of the cases identified were of traumatic origin, which allows the establishment of preventive and educational measures to avoid new cases of anophthalmia.

Combined Single Gene Testing and Genome Sequencing as an Effective Diagnostic Approach for Anophthalmia and Microphthalmia Patients.

Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more than half of A/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with A/M from Pakistani cohort and an unknown molecular basis. Single gene testing of FOXE3 was performed, followed by genome sequencing for unsolved probands in order to establish a genetic diagnosis for these families. All seven families were provided with a genetic diagnosis. The identified variants were all homozygous, classified as (likely) pathogenic and present in an A/M-associated gene. Targeted FOXE3 sequencing revealed two previously reported pathogenic FOXE3 variants in four families. In the remaining families, genome sequencing revealed a known pathogenic PXDN variant, a novel 13bp deletion in VSX2, and one novel deep intronic splice variant in PXDN. An in vitro splice assay was performed for the PXDN splice variant which revealed a severe splicing defect. Our study confirmed the utility of genome sequencing as a diagnostic tool for A/M-affected individuals. Furthermore, the identification of a novel deep intronic pathogenic variant in PXDN highlights the role of non-coding variants in A/M-disorders and the value of genome sequencing for the identification of this type of variants.

Efficacy of Systematic Early-Second-Trimester Ultrasound Screening for Facial Anomalies: A Comparison between Prenatal Ultrasound and Postmortem Findings.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

Management of external ocular prosthesis by ocularists: results of an online survey conducted in Brazil and Spain.

PURPOSE: To analyse the ocularist's perspective on the management of the anophthalmic socket and external ocular prosthesis (EOP). METHODS: Ocularists from two countries were invited to participate in an online questionnaire. Data were collected on demographics, anophthalmic socket and EOP management (manufacturing, use, cleaning), complications, follow-up visits and multidisciplinary care. The frequency and proportions of the responses were statistically analysed. RESULTS: The questionnaire was addressed to 20 Brazilian and 17 Spanish ocularists, obtaining a response rate of 65% and 64.7%, respectively. 62.5% of respondents were men. The most common cause of anophthalmia in Brazil (69.2%) and Spain (36.4%) is an eye disease (chi square: p = 0.188). Polymethylmethacrylate (PMMA) is the most commonly used material in EOP manufacture (chi square: p = 0.448), and 70.8% reported using customized EOPs (chi square: p = 0.069). Deposits are frequently observed in both countries (chi square: p = 0.157). Changing the prosthesis is recommended after 5 to 10 years by Brazilian ocularists, and after less than 5 years of use by Spanish ocularists (81.8%) (chi square: p = 0.041). Annual follow-up is recommended by Spanish ocularists (45.5%), while semestral (38.5%) and case-dependent (38.5%) follow-up is recommended by Brazilian ocularists (chi square: p = 0.267). Daily cleaning is advocated by 61.5% of Brazilian ocularists and once a month by 45.5% of Spanish ocularists (chi square: p = 0.098), with 75% of ocularists from both countries not recommending EOP removal at night (Fisher´s exact test: p = 0.166). Good communication between ocularists and ophthalmologists was reported by 87.5% of our responders (chi square: p = 0.642). CONCLUSION: Although there are no unified protocols on the management of EOPs, Brazilian and Spanish ocularists follow similar guidelines. Differences between countries were the patients´ referral and the prosthesis´ useful life.

SOX2 pathogenic variants with normal eyes: Expanding the phenotypic spectrum.

SOX2 pathogenic variants, though rare, constitute the most commonly known genetic cause of clinical anophthalmia and microphthalmia. However, patients without major ocular malformation, but with multi-system developmental disorders, have been reported, suggesting that the range of clinical phenotypes is broader than previously appreciated. We detail two patients with bilateral structurally normal eyes along with 11 other previously published patients. Our findings suggest that there is no obvious phenotypic or genotypic pattern that may help set apart patients with normal eyes. Our patients provide further evidence for broadening the phenotypic spectrum of SOX2 mutations and re-appraising the designation of SOX2 disorder as an anophthalmia/microphthalmia syndrome. We emphasize the importance of considering SOX2 pathogenic variants in the differential diagnoses of individuals with normal eyes, who may have varying combinations of features such as developmental delay, urogenital abnormalities, gastro-intestinal anomalies, pituitary dysfunction, midline structural anomalies, and complex movement disorders, seizures or other neurological issues.

Congenital bilateral clinical anophthalmia and brachygnathia superior in a fighting bull calf.

This study describes a case of a 20-day-old male fighting bull with bilateral clinical anophthalmia and brachygnathia superior whose dam was 12.5 years old and was mistakenly dewormed with ivermectin intramuscularly in the first third of gestation in a livestock farm. A macroscopic examination of the carcass was performed, with a special focus on the ocular components. Eyeball remains were found in both orbits and a histopathological examination was performed on them. Antibodies by serological study against bovine herpes virus-1, respiratory syncytial virus and bovine viral diarrhea virus for both the cow and the calf were not detected. The calf had small orbits and inside them a white and brown mass of soft consistency. Microscopically, abundant muscular and adipose tissue was observed, alongside nervous structures and vestiges of ocular structures with stratified epithelium and abundant connective tissue with glands. No evidence that this congenital bilateral anophthalmia had infectious or hereditary origin was found. By contrast, the malformation could be related to the treatment with ivermectin during the first month of gestation.

Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service.

Purpose: Hereditary causes are an important etiological category of childhood blindness. This study reports the real-world experience of a developing ocular genetic service. Methods: The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North-West India. Children presenting to the genetic clinic with congenital or late-onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel-based sequencing/chromosomal microarray) was outsourced to third-party laboratories with the cost of the test being borne by the patient. Results: Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Conclusion: Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Conjunctival sac microbiome in anophthalmic patients: Flora diversity and the impact of ocular prosthesis materials.

Purpose: To explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials. Methods: A cross-sectional clinical study was conducted, involving 19 OP patients and 23 healthy subjects. Samples were collected from the upper, lower palpebral, caruncle, and fornix conjunctiva. 16S rRNA sequencing was applied to identify the bacterial flora in the samples. The eye comfort of each OP patient was determined by a questionnaire. In addition, demographics information of each participant was also collected. Results: The diversity and richness of ocular flora in OP patients were significantly higher than that in healthy subjects. The results of flora species analysis also indicated that in OP patients, pathogenic microorganisms such as Escherichia Shigella and Fusobacterium increased significantly, while the resident flora of Lactobacillus and Lactococcus decreased significantly. Within the self-comparison of OP patients, compared with Polymethyl Methacrylate (PMMA), prosthetic material of glass will lead to the increased colonization of opportunistic pathogens such as Alcaligenes, Dermabacter and Spirochaetes, while gender and age have no significant impact on ocular flora. Conclusions: The ocular flora of OP patients was significantly different from that of healthy people. Abundant colonization of pathogenic microorganisms may have an important potential relationship with eye discomfort and eye diseases of OP patients. PMMA, as an artificial eye material, demonstrated potential advantages in reducing the colonization of opportunistic pathogens.

Identification of Novel Coloboma Candidate Genes through Conserved Gene Expression Analyses across Four Vertebrate Species.

Ocular coloboma (OC) is a failure of complete optic fissure closure during embryonic development and presents as a tissue defect along the proximal-distal axis of the ventral eye. It is classed as part of the clinical spectrum of structural eye malformations with microphthalmia and anophthalmia, collectively abbreviated to MAC. Despite deliberate attempts to identify causative variants in MAC, many patients remain without a genetic diagnosis. To reveal potential candidate genes, we utilised transcriptomes experimentally generated from embryonic eye tissues derived from humans, mice, zebrafish, and chicken at stages coincident with optic fissure closure. Our in-silico analyses found 10 genes with optic fissure-specific enriched expression: ALDH1A3, BMPR1B, EMX2, EPHB3, NID1, NTN1, PAX2, SMOC1, TENM3, and VAX1. In situ hybridization revealed that all 10 genes were broadly expressed ventrally in the developing eye but that only PAX2 and NTN1 were expressed in cells at the edges of the optic fissure margin. Of these conserved optic fissure genes, EMX2, NID1, and EPHB3 have not previously been associated with human MAC cases. Targeted genetic manipulation in zebrafish embryos using CRISPR/Cas9 caused the developmental MAC phenotype for emx2 and ephb3. We analysed available whole genome sequencing datasets from MAC patients and identified a range of variants with plausible causality. In combination, our data suggest that expression of genes involved in ventral eye development is conserved across a range of vertebrate species and that EMX2, NID1, and EPHB3 are candidate loci that warrant further functional analysis in the context of MAC and should be considered for sequencing in cohorts of patients with structural eye malformations.

Optic cup morphogenesis across species and related inborn human eye defects.

The vertebrate eye is shaped as a cup, a conformation that optimizes vision and is acquired early in development through a process known as optic cup morphogenesis. Imaging living, transparent teleost embryos and mammalian stem cell-derived organoids has provided insights into the rearrangements that eye progenitors undergo to adopt such a shape. Molecular and pharmacological interference with these rearrangements has further identified the underlying molecular machineries and the physical forces involved in this morphogenetic process. In this Review, we summarize the resulting scenarios and proposed models that include common and species-specific events. We further discuss how these studies and those in environmentally adapted blind species may shed light on human inborn eye malformations that result from failures in optic cup morphogenesis, including microphthalmia, anophthalmia and coloboma.