Congenital Corneal Staphyloma: A Comprehensive Histopathologic Assessment Including Associated Anterior Segment Abnormalities.

Congenital corneal staphyloma is a rare congenital malformation with guarded visual potential. The cornea is opaque, markedly ectatic, and lined by uveal tissue with a variety of associated anterior segment abnormalities. In this case report, the detailed histopathology of this condition is highlighted with an unusual finding of the malformed lens. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e28-e32.].

Amniotic bands as a cause of congenital anterior staphyloma.

BACKGROUND: Congenital anterior staphyloma is a rare, complex malformation syndrome of the anterior segment. Only a few reports on associated systemic malformations have been published. We herein present a rare manifestation of congenital anterior staphyloma (CAS) combined with amniotic band disruption syndrome (ABS). PATIENT AND METHODS: Shortly after birth, a massive enlargement of the left eye was observed in a female child. Furthermore, an extensive bilateral congenital cleft lip and cleft alveolar ridge with oblique facial cleft extending into the left medial canthal region, coloboma(s) of the left eyelids, extensive adhesions between lids and eye bulb, as well as circumferential grooves, clubfeet, and terminal transverse defects in both hands and feet were present. Due to severe progression of eye bulb protrusion with thinning of the sclera, enucleation of the left eye was performed at the age of 3 years in order to prevent complications including perforation of the globe and with the aim of improving cosmetic aspects. RESULTS: Histopathological examination of the enucleated eye disclosed findings typical of congenital anterior staphyloma, including massive corneal staphylomatic deformation with superficial vascularization and elapsed corneoscleral margin, destruction of Bowman's layer, absence of Descemet's layer, corneal endothelium, and angle structures. The lens was only partially formed, and had mainly dissolved. The neural retina appeared normal. The optic nerve disc revealed a pronounced excavation. Facial clefts, lid colobomas, congenital constriction bands, and amputation of distal limbs match ABS. This malformation complex develops in early pregnancy, probably prior to 35 days post conception. CONCLUSION: This is the first report on an association of these two rare complex congenital malformations, congenital anterior staphyloma and amniotic band syndrome. The anterior staphyloma was unilateral, and related to facial clefts and lid coloboma in the area adjacent to the anterior staphyloma. Furthermore, the systemic deformities are clearly due to the amniotic bands, and the timing of the development of both complex malformations seems to be similar. All findings suggest that the presence of amniotic bands is a causative factor for all observed abnormalities including anterior staphyloma.

A nonsense mutation of CRYGC associated with autosomal dominant congenital nuclear cataracts and microcornea in a Chinese pedigree.

PURPOSE: To report the identification of a nonsense mutation in γC-crystallin (CRYGC) associated with autosomal dominant congenital nuclear cataracts and microcornea in a Chinese family. METHODS: We investigated four generations of a Chinese family six of whose members were affected by nuclear cataracts and microcornea. The genomic DNA was extracted from peripheral blood leukocytes. All reported nuclear cataract-related candidate genes were screened for causative mutations by direct DNA sequencing. The effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis. RESULTS: All affected individuals in this family exhibited nuclear cataracts and microcornea. Direct sequencing of the candidate gene cluster showed a c.471G>A transition in exon 3 of CRYGC, which co-segregated according to family members with cataracts, and was not observed in 100 normal controls. This single nucleotide change was predicted to introduce a translation stop codon at tryptophan 157 (W157X). Bioinformatics analysis showed that the mutation was predicted to affect the function and secondary structure of the CRYGC protein. CONCLUSIONS: This study identified a disease-causing mutation c.471G>A in CRYGC in a Chinese family with cataracts, expanding the mutation spectrum of CRYGC causing congenital cataracts.

Congenital corneal staphyloma as a complication of Kabuki syndrome.

Kabuki syndrome has long been clinically defined based mainly on its characteristic eye features. The recent discovery of MLL2 as a causative gene of Kabuki syndrome has enabled the extreme end of the phenotype to be explored. We herein report on two patients with striking visible congenital staphyloma at birth. A diagnosis of Kabuki syndrome was subsequently made in both patients based on a constellation of characteristic eye features, cardiac abnormalities and severe developmental delay, and finally by the confirmation of MLL2 mutations. In conclusion, congenital corneal staphyloma is a complication of Kabuki syndrome with MLL2 mutations.

A novel mutation in CRYBB1 associated with congenital cataract-microcornea syndrome: the p.Ser129Arg mutation destabilizes the ßB1/ßA3-crystallin heteromer but not the ßB1-crystallin homomer.

Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [θ]=0.0), which closely flanks the â-crystallin gene cluster locus. Direct sequencing of the candidate âB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant ß-crystallins revealed that the mutation impaired the structures of both ßB1-crystallin homomer and ßB1/ßA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of ßB1/ßA3-crystallin but not ßB1-crystallin. These findings highlight the importance of protein-protein interactions among ß-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC.

Mutational screening of six genes in Chinese patients with congenital cataract and microcornea.

PURPOSE: To identify mutations in 6 genes of 9 Chinese families with congenital cataract and microcornea. METHODS: Nine unrelated families with congenital cataract and microcornea were collected. Cycle sequencing was used to detect variants in the coding and adjacent regions of the crystallin alpha A (CRYAA), crystallin beta B1 (CRYBB1), crystallin beta A4 (CRYBA4), crystallin gamma C (CRYGC), crystallin gamma D (CRYGD), and gap junction protein alpha 8 (GJA8) genes. RESULTS: Upon complete analysis of the 6 genes, three mutations in 2 genes were detected in 3 families, respectively. These mutations were not present in 96 normal controls. Of the three mutations, two novel heterozygous mutations in GJA8, c.136G>A (p.Gly46Arg) and c.116C>G (p.Thr39Arg), were found in two families with congenital cataract and microcornea. The rest one, a heterozygous c.34C>T (p.Arg12Cys) mutation in CRYAA, was identified in three patients from a family with nuclear cataract, microcornea with axial elongation. No mutation in the 6 genes was detected in the remaining 6 families. CONCLUSIONS: Mutations in GJA8 and CRYAA were identified in three families with cataract and microcornea. Elongation of axial length accompanied with myopia was a novel phenotype in the family with the c.34C>T mutation in CRYAA. Our results expand the spectrum of GJA8 mutations as well as their associated phenotypes.

Ramos-Arroyo syndrome: confirmation of an entity.

In 1987, Ramos-Arroyo et al. described a family with a previously unreported combination of features, which included corneal anesthesia, short stature, sensorineural deafness, learning difficulties, and a characteristic facial appearance. The family was reviewed in 2008 and additional features were noted. The name Ramos-Arroyo syndrome was proposed. The condition can be delineated by corneal anesthesia, absence of the peripapillary choriocapillaris and retinal pigment epithelium, bilateral sensorineural hearing loss, unusual facial appearance, persistent ductus arteriosus, Hirschprung disease, short stature, and intellectual disability. No other patient has been described since. Here, we report on a 5-year-old girl with features consistent with Ramos-Arroyo syndrome. We propose an overlap of this condition with dysautonomia syndromes.

Congenital cystic eye: from prenatal diagnosis to therapeutic management and surgical treatment.

Only 28 cases of congenital cystic eye have been reported in the literature. The main issue in such cases is differential diagnosis between this malformation and different cystic malformations and masses of the orbital cavity and eyeball, the most common of which is microphthalmia with cyst. Both malformations arise from incomplete closure of the fetal optic vesicle in different stages of embryonic development. We present a case of congenital cystic eye, associated with coloboma and corneal dermoid of the fellow eye and with left brachiocephaly, discussing differential diagnosis with microphthalmia with cyst and illustrating the treatment we planned and performed. The patient first underwent a surgical excision of the left corneal dermoid, then a resection of the right orbital cyst. The last step was to perform a craniotomy and cranial vault remodeling. All the operations were planned and performed using a team approach. The team comprised an ophthalmologist, a plastic surgeon, and a neurosurgeon, and the result was a successful outcome.

Clinical spectrum of congenital corneal staphyloma: a case report.

We report the dramatic ophthalmological findings in a newborn baby consisting of a perforated right eye and a protruding buphthalmic opacified left eye. The diagnosis of congenital corneal staphyloma was suspected and was confirmed on histopathological examination of the right eye remnants, and of the left cornea after a corneoscleral keratoplasty was performed. This case report describes one clinical spectrum of Peter's anomaly.

[CRYAA gene mutation study in a family with autosomal dominant congenital cataract combined with microcornea].

OBJECTIVE: To identify the gene mutation in a four-generation Chinese family with autosomal dominant congenital cataract associated with microcornea. METHODS: Experimental research. Twelve members in this family (including six affected and six unaffected individuals) were enrolled into this study. They underwent full ophthalmological and clinical examinations to rule out any concomitant disorders. Blood samples were collected and genomic DNA was extracted. Microsatellite markers near the reported loci, which are associated with congenital cataract and microcornea were selected and amplified from DNA samples using polymerase chain reaction. Linkage analysis was performed. The exons and exon/intron junction of candidate gene in the related chromosome were sequenced. The product of the first exon was digested by ApaL I restriction enzyme to certify the mutation. RESULTS: The phenotype studied in this family was nuclear cataract accompanied with microcornea. At markers D21S1885 and D21S1890 near the locus 21q22.3, the affected members had the same allele, but the unaffected did not. The Lod scores were 2.11 in both markers, indicating that this locus were linked to the congenital cataract in this family. DNA sequencing of candidate gene CRYAA showed a heterozygous mutation c.34C > T in exon 1, which led to condon 12 in peptide chain encoding arginine substituted by cysteine. ApaL I enzyme digestion certified that all of the affected members had the same mutation c.34C > T, but the unaffected and normal individuals did not. CONCLUSION: Mutation (p.R12C) of CRYAA is the genetic change that causes the occurrence of congenital cataract with microcornea in this family.

[Congenital corneal staphylomas in children].

Clinical manifestation, results and outcomes of surgical treatment were studied in children with very rare anomaly of cornea and anterior segment. Symptoms and signs, histological findings are described in details, results of ophthalmoscopy, ultrasound biomicroscopy and maternal ophthalmotrophic infections are studied in children with corneal staphylomas.

Clinical and confocal imaging findings in congenital corneal anaesthesia.

BACKGROUND/AIMS: Congenital corneal anaesthesia (CCA) is an uncommon cause of corneal ulceration in young patients, with a reported poor visual prognosis. We correlated clinical findings in patients with CCA with corneal sub-basal nerve plexus (SBNP) morphology and dendritiform cell density (DCD) on confocal microscopy. METHODS: A prospective, case-control study was conducted at a referral clinic. History includied presenting features in patients with CCA, clinical course and examination findings. Differences in SBNP morphology and DCD on in vivo confocal microscopy (IVCM) were compared in cases and control subjects with healthy corneas. RESULTS: Eight patients with CCA were examined, of which three had a diagnosis of familial dysautonomia. Age at initial diagnosis of corneal disease ranged from infancy to 22 years, the most common presentation being corneal ulceration. All patients with CCA except one with optic neuropathy had corrected visual acuity 6/18 (logMAR 0.35) or better in at least one eye. Measured corneal sensation was minimal in all patients. Major abnormalities were found on confocal microscopy in all patients with CCA, whether or not inherited, including statistically significant reduction in SBNP nerve fibre density, fibre length and branch density. Increased DCD in superficial cornea was found in all patients with CCA. CONCLUSION: Good visual acuity can be maintained in eyes with corneal anaesthesia present from birth. IVCM provides direct evidence of a morphological correlate for measured corneal anaesthesia. Increased DCD may indicate an enhanced role for innate immune cells in superficial cornea in protection of the anaesthetic ocular surface.

Surgical therapy of unusual congenital corneal fibroma.

Surgical removal of left congenital limbo corneal mass by peripheral lamellar keratoplasty (LKP) using preserved remaining corneasclera graft from other recipient was effective for the treatment of limbocorneal fibroma. A case of 17 year old Chinese girl with a corneal mass since her birth on 4:00 'O clock position showed a size of about 2-3 mm. The patient was treated with total resection of the mass with part of Corneascleral Limbus and partial cornea with adjacent tissue and was diagnosed as fibroma after histopathology examination. After follow-up for 6 month, the vision and eye ball movements were normal and the graft was in normal position.

Histopathological examination of congenital corneal staphyloma and prognosis after penetrating keratoplasty.

The aim of this study was to investigate the histopathological manifestations of congenital corneal staphyloma accompanied by anterior segment dysgenesis and evaluate the prognosis after penetrating keratoplasty with an ultralarge button graft.We retrospectively studied 8 pediatric patients with large congenital corneal staphylomas in the Department of Ophthalmology of Peking University Third Hospital, China, between September 2014 and December 2018. All patients underwent penetrating keratoplasty with ultralarge button grafts, as well as additional operations according to the abnormality of each eye. Pathological investigations of all samples obtained during penetrating keratoplasty were performed with hematoxylin and eosin staining.The main clinical characteristic of congenital corneal staphyloma was an extremely opaque and ectatic cornea. Histopathological examination showed abnormal corneal epithelia and stroma and an absence of Bowman membrane, Descemet membrane, and the endothelium. Different severities of anterior segment dysgenesis, presenting as various histopathological manifestations, were observed in all cases. Several postoperative complications occurred after penetrating keratoplasty in some of the patients; however, the complications were discovered and treated accordingly in a timely manner. Six patients achieved good visual outcomes and a satisfactory cosmetic appearance after penetrating keratoplasty. One patient eventually lost the transparency of the button because of corneal neovascularization, and 1 patient lost visual function because of retinal detachment.Congenital corneal staphyloma combined with anterior segment dysgenesis can exhibit various manifestations on histopathological examination. Penetrating keratoplasty with an ultralarge button graft seems to be a suitable treatment for congenital corneal staphyloma to obtain good functional and aesthetic prognoses.

Corneal anomalies in newborn primary congenital glaucoma.

This report describes the corneal pathology in an infant with newborn primary congenital glaucoma and discusses whether these findings could be due to a developmental anomaly. The corneal specimen of a 4-month-old infant with newborn primary congenital glaucoma and cloudy corneas who had undergone penetrating keratoplasty was evaluated by light and electron microscopy. Light microscopy showed a thinned epithelium, areas of thickened Bowman's layer (approximately 27 mum thick) interspersed with nuclei, and a thickened and disorganized stroma. Descemet's membrane was intact, and the endothelium was mildly attenuated. The corneal changes seen in this patient may be specific to primary congenital glaucoma and may contribute to the corneal clouding seen so frequently in these patients.

Microcornea, Posterior Megalolenticonus, Persistent Fetal Vasculature, and Coloboma Syndrome Associated With a New Mutation in ZNF408.

The authors report a case of a 6-week-old girl with microphthalmia, posterior lenticonus, persistent fetal vasculature, and coloboma of the right eye, with morning glory disc anomaly and falciform retinal folds of the left eye. Genetic testing revealed a previously unreported mutation (c.1471A>G [p.T491A]) in the gene ZNF408, which has been associated with autosomal recessive retinitis pigmentosa and autosomal dominant familial exudative vitreoretinopathy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:253-256.].

Congenital corneal staphyloma treated by evisceration and primary implant placement: 3 cases.

BACKGROUND: We report 3 cases of congenital corneal staphyloma. METHODS: Two cases were cosmetically treated by evisceration and primary implant insertion and 1 case spontaneously converted to phthisis bulbi. RESULTS: Placement of a cosmetic prosthesis improved the external appearances in the first 2 cases. No complications after operation were noted. The final outcome in the third patient was phthisis bulbi, which occurred spontaneously at 5 years of age in the absence of any surgery. INTERPRETATION: Evisceration with primary implant insertion is an appropriate treatment modality for congenital corneal staphyloma.

Surgical Outcome of Congenital Cataract in Eyes With Microcornea.

PURPOSE: To report the intraoperative and postoperative outcomes of congenital cataract surgery in eyes with microcornea. METHODS: In this retrospective, interventional, comparative case series, the authors reviewed 47 eyes of 26 children with microcornea and congenital cataract (21 bilateral and 5 unilateral) who underwent lens aspiration with primary posterior capsulectomy and anterior vitrectomy between 2008 and 2014 with a minimum follow-up period of 6 months. Demographic profiles and systemic and ocular features were documented. Intraoperative and postoperative complications were studied separately for bilateral and unilateral cases. Patients were also divided into two groups on the basis of their ages at surgery (early surgery group: 3 months or younger; late surgery group: older than 3 months) and postoperative complications were compared. Visual outcome was analyzed in those with a follow-up period of more than 1 year. RESULTS: Early surgery was performed in 24 eyes of 13 patients (11 bilateral and 2 unilateral) and late surgery in 23 eyes of 13 patients (10 bilateral and 3 unilateral). Intraoperatively, all eyes had poor pupillary dilatation and 6 (12.8%) eyes needed iris hooks. Postoperatively, the most common early complication was transient corneal edema observed in 22 (46.8%) eyes (13 and 8 eyes in the early and late surgery groups, respectively). Late complications included visual axis opacification in 6 (12.76%) eyes (3 in each group), and secondary glaucoma in 5 (10.64%) eyes (2 and 3 eyes in the early and late surgery groups, respectively). Vision was normal for age in 18 (60%) of the bilateral cases with a follow-up period of more than 1 year. CONCLUSIONS: Early surgical intervention for congenital cataract in eyes with microcornea can result in favorable outcomes with an acceptable rate of postoperative complications. [J Pediatr Ophthalmol Strabismus. 2018;55(1):30-36.].

Corneal Abnormalities in Congenital Aniridia: Congenital Central Corneal Opacity Versus Aniridia-associated Keratopathy.

PURPOSE: To clinically characterize and compare 2 types of corneal abnormalities in patients with congenital aniridia: (1) congenital central corneal opacity from birth (CCO) and (2) aniridia-associated keratopathy (AAK) that develops progressively with age. DESIGN: Retrospective cohort study. METHODS: Medical records of Korean patients who were diagnosed with congenital aniridia at Seoul National University Hospital between 1991 and 2016 were reviewed. Prevalence of corneal abnormalities (CCO and AAK), other ocular and systemic comorbidities, severity of AAK depending on the age, logarithm of the minimum angle of resolution (logMAR) visual acuities, and types and results of surgical intervention were collected. RESULTS: Among a total of 275 eyes (138 patients), 13% (35 eyes, 20 patients) had CCO and 25% (68 eyes, 35 patients) developed AAK. The AAK became prominent at a mean of 21.6 years of age, and the severity progressed with age. Glaucoma was more prevalent in aniridia patients with CCO (74%), compared to those with AAK (37%) (P = .0003). Cataract frequently occurred in patients with AAK (78%), who required cataract surgeries at mean 26.6 years. The logMAR visual acuity was worse in patients with CCO (2.04 ± 0.71) than in those with AAK (1.29 ± 0.62) (P < .0001). Penetrating keratoplasty was performed in 6 eyes with CCO, and the graft survival was 33.3% during mean 45 months of follow-up (range 14-79 months). CONCLUSIONS: In total, 13% of aniridia patients had CCO at birth, while 25% progressively developed clinically significant AAK with age. The visual outcome was worse in patients with CCO than in those with AAK.

Analysis of KERA in four families with cornea plana identifies two novel mutations.

PURPOSE: To identify the molecular genetic cause in four families of various ethnic backgrounds with cornea plana. METHODS: Detailed ophthalmological examination and direct sequencing of the KERA coding region in five patients of Czech and Turkish origin and their available family members. RESULTS: Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887-1G>A in KERA were detected in two affected siblings of Czech origin. In silico analysis supported the pathogenicity of both variants. The second proband of Czech origin harboured c.835C>T; p.(Arg279*) in a homozygous state. Homozygous mutations c.740A>G; p.(Asn247Ser) and c.674C>T; p.(Ile225Thr) were identified in the Turkish probands, both born out of consanguineous marriages. Observed ocular phenotypes were typical of cornea plana with the exception of one Czech patient who also had marked thinning and protrusion in the superior part of the left cornea (mean keratometry 47.2 D). No corneal endothelial cell pathology was found by specular microscopy in seven eyes, in three eyes visualization of the posterior corneal surface was unsuccessful. CONCLUSION: KERA mutation c.740A>G has been identified to date in three different populations, which makes it the most frequently occurring mutation in patients with cornea plana. Marked corneal thinning and ectasia are a very rare finding in this disorder and longitudinal follow-up needs to be performed to determine its potential progressive nature.