Table 1 - uploaded by Nicola K Ragge
Content may be subject to copyright.
Source publication
Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. They often arise in conjunction with other ocular defects such as coloboma and orbital cyst. They may also be part of more generalised syndromes, such as CHARGE syndrome. Anophthalmia, microphthalmia, and coloboma are likely to be caused by disturbances of the m...
Context in source publication
Context 1
... some individuals with anophthalmia or microphthalmia have relatives with other eye malformations, the frequent lack of clear Mendelian inheritance in these conditions has made identifying the genes for eye development very challenging. However, using a variety of techniques, some genes involved in anophthalmia or microphthalmia have now been identified (see Table 1). These include genes principally involved in ocular development, such as CHX10, many of which are involved in the development of substructures within the eye 19,21 and genes that are involved in eye and brain development including SOX2, OTX2, and PAX6. ...
Similar publications
Goldenhar syndrome (oculo-auriculo-vertebral dysplasia, OAVS) is a rare, congenital disease arising from the abnormal development of the first and second branchial arches.
The incidence is between 1:3500 and 1:5600, with a male: female ratio of 3:2. The etiopathogenesis is multifactorial and dependent on genetic and environmental factors but there...
Purpose
. The goal was to describe our experience in the surgical management and treatment of four patients with congenital upper eyelid colobomas.
Methods
. A descriptive, observational, retrospective study was performed including patients with congenital eyelid colobomas referred to Asociación para Evitar la Ceguera en México I.A.P. “Dr. Luis Sán...
Purpose:
To review the recent literature and describe the authors' experience with congenital upper eyelid coloboma.
Methods:
In this review, we will summarize the embryologic and etiopathogenetic bases of congenital upper eyelid coloboma, and study the published clinical reports. We will also attempt to briefly shed some light on the rarer synd...
Citations
... Microphthalmos is a rare structural eye malfunction resulting from abnormalities in the development of the primary optic vesicle [1]. It has an incidence of 0.2-9 per 10,000 births, affects 3-11% of blind children, and is associated with a high prevalence of congenital cataracts [2][3][4][5]. ...
Purpose
To investigate the postoperative clinical outcomes and axial length (AL) growth of infants with congenital cataracts and microphthalmos following first-stage cataract surgery.
Design
Retrospective case-control study.
Methods
Setting: Single centre. Infants with congenital cataract that met the inclusion criteria were classified into two groups: the microphthalmos and comparison groups. All infants underwent a thorough ophthalmologic examination before surgery, and one week, 1 month, 3 months, and every 3 months after surgery.
Results
This study enrolled 21 infants (42 eyes) in the microphthalmos group and 29 infants (58 eyes) in the comparison group. More glaucoma-related adverse events were observed in the microphthalmos group (7 eyes, 16.7%) than in the comparison group (0 eyes, 0%) ( p < 0.001). At each subsequent follow-up, the comparison group had a greater AL than the microphthalmos group (all p < 0.001), and AL growth was significantly higher in the comparison group than in the microphthalmos group (all p = 0.035). Visual acuity improvement in the microphthalmos group was similar to that of the comparison group.
Conclusion
Early surgical intervention improves visual function in infants with congenital cataracts and microphthalmos although with a higher incidence of glaucoma-related adverse events. After cataract removal, the AL growth of microphthalmic eyes is slower than that of normally developed eyes.
... Peters anomaly is a rare congenital eye condition characterized by anterior segment dysgenesis and corneal opacity (leukoma), with or without associated craniofacial or skeletal anomalies (Fig. 4) [14]. Management includes ophthalmology referral for consideration of surgery to allow visual development [15]. ...
Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.
Graphical Abstract
... This is a rare developmental disorder affecting one in 5000 individuals [48] where one or both eyes are abnormally small with an axial diameter less than 2SD below the mean for age. Microphthalmia may be associated with microcornea, aniridia, cataract, and retinal degeneration [49]. ...
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common birth defects worldwide and a major cause of kidney failure in children. Extra-renal manifestations are also common. This study reviewed diseases associated with the Genomics England CAKUT-associated gene panel for ocular anomalies. In addition, each gene was examined for expression in the human retina and an ocular phenotype in mouse models using the Human Protein Atlas and Mouse Genome Informatics databases, respectively. Thirty-four (54%) of the 63 CAKUT-associated genes (55 'green' and 8 'amber') had a reported ocular phenotype. Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract. Seven of the CAKUT-associated genes studied (11%) had no reported ocular features but were expressed in the human retina or had an ocular phenotype in a mouse model, which suggested further possibly-unrecognised abnormalities. About one third of CAKUT-associated genes (18, 29%) had no ocular associations and were not expressed in the retina, and the corresponding mouse models had no ocular phenotype. Ocular abnormalities in individuals with CAKUT suggest a genetic basis for the disease and sometimes indicate the affected gene. Individuals with CAKUT often have ocular abnormalities and may require an ophthalmic review, monitoring, and treatment to preserve vision.
... Complete anophthalmia is uncommon, and some residual ocular tissue may often be identified through post-mortem examination. [4][5][6] Canine ocular development begins around the third week of pregnancy, and there are many opportunities for occurring developmental malformations in the fetal period. Three fetal tissues are involved in the normal development of the eyes: surface ectoderm of the head, mesenchymal tissue of neural crest origin, and neuroectoderm of the forebrain. ...
... 11,4 Ultrasound, as the most accurate tool for diagnosing this congenital malformation, can be useful for evaluating the intraocular structures and the presence of residual ocular tissues. 3,6 In this study, we used the transpalpebral technique because it is easier to perform than the transcorneal technique, and the possibility of corneal damage is less. 1 Further studies are needed to understand the underlying causes of this significant congenital malformation in veterinary medicine. ...
Anophthalmia refers to the most severe ocular congenital malformation that results from inadequate development of the primitive forebrain and is always associated with blindness. The exact etiology of anophthalmia is not well understood; however, heritable and environmental factors may be involved. A 2-month-old Asian Shepherd puppy was presented with the absence of one eye. The puppy was alert, responsive, and had a good body score. The eyelids with eyelashes and palpebral conjunctiva were bilaterally present. However, in the right eye, the palpebral fissure was narrow, and the orbit was shallow without a distinct globe. Further inspection revealed no ocular structures, although the left eye was ophthalmoscopically quite normal. Also, there were no cytologic characteristics of conjunctivitis in either eye. Using the transpalpebral ultrasonography technique, a semi-oval anechoic area without any obvious ocular chambers or structures was observed in the right eye, and finally, unilateral clinical anophthalmia was diagnosed. General physical examination revealed no other malformation. The long-term prognosis is favorable for this pup. However, surgical strategies (e.g., implants and expanders) can be used to improve cosmetic appearance.
... Coloboma is a closure defect within the optic fissure, typically causing a "keyhole" shape within the iris, inferior lens irregularity, and an inferonasal defect in the retina and choroid layers of the eye, though patients may only exhibit the posterior findings. These eye malformations play a role in childhood visual impairment, with microphthalmia being present in up to 11% of blind children [11][12][13]. The prevalence of microphthalmia is approximated as one in 7000 live human births, one in 30,000 live births for anophthalmia, and one in 5000 live births for coloboma [14]. ...
Background:
Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.
Results:
Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.
Conclusions:
Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.
... Unilateral and bilateral findings may be isolated or associated with a variety of abnormalities and syndromes [6]. The diseases are caused by disorders in the morphogenesis of the eye [7]. These can be caused by genetic defects, such as the presence of chromosomal aberrations or monogenetic mutations [8], or by external influences that affect the processes of morphogenesis, such as intrauterine viral or toxoplasmosis infection or exposure to toxins during pregnancy [9]. ...
... At the Eye Clinic Rostock (Table 4, "Treatment at the University Eye Hospital"), the ophthalmologist discusses the condition with the parents and offers a treatment plan. Parents are understandably concerned about the condition, especially if the finding was not diagnosed prenatally [7]. This is also shown by the results of our study, in which 11 out of 21 parents were affected when they saw their child for the first time. ...
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.
... In a prospective epidemiological study in the UK, Shah et al. [8] did not differentiate NO from MO; inclusion was based on AL, where available, and physician discretion on clinical exam in the remainder. Similarly, Ragge et al. [9] grouped "small-eye" conditions together in terms of practical clinical management strategies. This again acknowledges that standardized classification within this spectrum of related conditions is lacking [8]. ...
... Genotype-driven deep phenotyping shows that this clinical grouping may represent multiple different embryonic eye growth pathways under one heading (e.g., colobomata are not seen in MFRP-associated NO as MFRP expression begins in the 2nd trimester), though there may be interaction between several regulatory mechanisms [5]. Such anomalies may occur in isolation or a part of a syndrome (up to 50%) such as "coloboma, heart defects, atresia of nasal choanae, growth retardation, genital, and ear abnormalities (CHARGE) syndrome" [9]. Shah et al. [8] report higher prevalence of NAMC amongst children of Pakistani and Bangladeshi ethnicity (X3.7 times higher risk) and suggest increased incidence is seen in the context of socioeconomic deprivation. ...
... Even without immediate, gene-therapy implications, optimizing visual potential (e.g., correction of refractive error, glaucoma screening), and treating symptomatic complications (e.g., cataract, CML), with molecular characterization as the cornerstone [3,15] leads to better outcomes. The ophthalmologist often coordinates multidisciplinary team input (i.e., ophthalmic physician/surgeon, molecular and clinical geneticists, genetic counsellors, other medical specialties as appropriate), efficient and equitable access to treatment, visual rehabilitation strategies, and genetic counselling for parents/families [8,9,15]. ...
The conjunction of nanophthalmos (NO) and retinitis pigmentosa (RP) provides challenges to effective clinical management while narrowing the genetic spectrum for targeted molecular diagnostics. This case study describes two not knowingly related adult cases of MFRP -associated retinopathy and nanophthalmos (MARN). Structural features including short axial lengths (mean 16.4 mm), steep keratometry (mean 49.98 D), adult-onset signs, and symptoms of retinal dystrophy and acquired disease (i.e., cataract, angle-closure glaucoma) were evident in both cases. Pathogenic variants in the MFRP gene impair both prenatal eye growth and childhood emmetropization while also leading to RPE/outer retinal degeneration in 75% of cases. We discuss the “small-eye” phenotype spectrum and associated defining characteristics, molecular mechanisms with particular focus on MFRP-associated NO with RP features (MARN), the spectrum of visual morbidities (e.g., extreme refractive error, amblyopia, cystoid macular lesions, early cataract) and the challenges of their treatment/surgical management.
... Reports have shown that although microphthalmia affects 3.2-11.2% of blind children, there is no treatment available to improve patients' eyesight. Current management is focused on maximizing the present vision and improving cosmetic appearance [156][157][158]. Microphthalmia is frequently accompanied by additional ocular abnormalities such as anterior segment dysgenesis, ocular coloboma, cataract, or vitreoretinal dysplasia and exhibits considerable clinical heterogeneity [157]. ...
Retinal organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that mimic the retina's spatial and temporal differentiation, making them useful as in vitro retinal development models. Retinal organoids can be assembled with brain organoids, the 3D self-assembled aggregates derived from hPSCs containing different cell types and cytoarchi-tectures that resemble the human embryonic brain. Recent studies have shown the development of optic cups in brain organoids. The cellular components of a developing optic vesicle-containing or-ganoids include primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. The importance of retinal organoids in ocular diseases such as age-related macular degeneration, Stargardt disease, retinitis pigmentosa, and diabetic retinopathy are described in this review. This review highlights current developments in retinal organoid techniques, and their applications in ocular conditions such as disease modeling, gene therapy, drug screening and development. In addition, recent advancements in utilizing extracellular vesicles secreted by retinal organoids for ocular disease treatments are summarized.
... N anophthalmos manifests as a short axial length (AL) with a short anterior chamber depth (ACD) and is defined as AL < 20 mm to 21 mm without other structural abnormalities. 1 , 2 While relative anterior microphthalmos (RAM) shows a disproportionately shallow anterior chamber with normal AL, its diagnostic base is a corneal diameter < 11 mm and an aqueous depth < 2.2 mm. 1 , 2 Both belong to the clinical spectrum of microphthalmos, a congenital deficiency in primary optic vesicle development. 3 Due to the pathological features, patients with nanophthalmos or RAM tend to undergo cataract surgery at an earlier age. 4 To meet the demand for a preferable visual outcome, choosing the most appropriate formula to calculate IOL power is clinically significant in such cases. ...
Purpose
: To compare the prediction accuracy of 6 intraocular lens (IOL) formulas, namely, the Haigis, Hoffer Q, Holladay I, SRK/T, Barrett Universal II and Hoffer QST formulas, in microphthalmic eyes, including those with nanophthalmos and relative anterior microphthalmos (RAM).
Design
: A retrospective case series.
Methods
: Twenty-six eyes with nanophthalmos (axial length (AL): 16.84±1.36 mm, range 15.25 mm-19.82 mm) and 12 eyes with RAM (corneal diameter: 8.41±0.92 mm, range 7.00 mm-9.50 mm) receiving cataract surgery were included. The IOL Master 500 was used for biometry; thus, lens thickness (LT) was omitted in the IOL power calculation. The mean and median arithmetic and absolute prediction errors (PEs) of the 6 original calculation formulas, the absolute PEs of the 6 formulas after optimization, and the proportion of PEs within ±0.25 D, ±0.5 D, ±1 D and ±2 D with each formula were compared. The factors influencing PE were analyzed by multivariate regression.
Results
: In the nanophthalmos group, the overall prediction results were shifted to myopia. The original Haigis formula had the smallest median absolute PE (1.61 D, p<0.001), and the optimized Haigis formula had the highest proportion of PEs within ±0.25 D, ±0.5 D and ±1 D. In the RAM group, the overall prediction results were not significantly different from zero (p>0.05). No significant difference was found among the formulas before optimization (p=0.146) and after optimization (p=0.161), but the optimized Barrett Universal II formula had the highest proportion of PEs within ±1 D and ±2 D.
Conclusions
: When omitting the LT parameter in the calculation, the Haigis formula was the most accurate in cataract patients with nanophthalmos (AL<20 mm) among the 6 IOL calculation formulas, and the Barrett Universal II formula had the highest accuracy in cataract patients with RAM (corneal diameter≤9.5 mm).
... The two most important aspects are always considered for making a sufficient fornix to support the ocular prosthesis and make the adequate orbital volume. 3 There are multiple risk factors for developing a contracted socket, including failure to wear a prosthetic for a long time, infection in the ocular surface or orbital infection, post-radiation, excessive tissue damage due to trauma, extreme tissue manipulation or excessive excision of conjunctiva during enucleation or evisceration, and autoimmune diseases like mucous membrane pemphigoid, Stevens-Johson-Syndrome. [4][5][6] There are various classifications for the contracted socket. The soft tissue sockets have recently been divided into five grades to adopt an appropriate surgical plan. ...
... Lower fornix can be reconstructed by fornix deepening sutures with/without MMG or AMG. 2,5,6,[12][13][14] The popular technique of Lower fornix reconstruction by fornix deepening sutures with external bolster. The advantage of fornix deepening sutures with external bolster is an easy procedure and less learning curve but disadvantages like Blind procedure, the Recurrence rate is high, and causes ugly scar mark on the skin, and skin infection. ...
... New Approaches to lower fornix reconstruction are fornix deepening sutures without external bolster or internal fixation to the periosteum, and another technique is fornix reconstruction with harvesting fascia lata strip. [3][4][5]15 In our case series, the recurrence was 8% in the 351 cases of lower fornix reconstruction with external bolster. ...
