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The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

Dandy-Walker Syndrome (D-WS) is a rare disorder with an incidence of 1%–2% of all central nervous system anomalies. The diagnosis can be challenging, especially in the prenatal period. Here, we present an extremely rare case of D-WS associated with bilateral congenital cataracts. A 36 weeks and 6 days old male baby presented with a Dandy-Walker variant associated with bilateral congenital cataract. Ophthalmological examination revealed microphthalmos and congenital cataracts present in both eyes with sclerocornea, iris coloboma, and zone 3 retinopathy of prematurity involving only the right eye. However, the right eye was salvageable. Skull transillumination was negative with no cranial bruit. He was admitted to the neonatal intensive care unit with breathing difficulties, maintained SpO2 with oxygen through prongs, and noninvasive continuous positive airway pressure for 7 days. He had two episodes of hypoglycemia with hypothermia. There was no significant finding in sepsis evaluation. The abdominal ultrasonography was normal. Echocardiogram was suggestive of patent foramen ovale. Mother's torch panel tested positive for cytomegalovirus immunoglobulin G antibodies. Magnetic resonance imaging brain suggested variant D-WS with dilation of cerebellar fossa and occipital lateral ventricle horn and lack of usual corpus callus structure. Intravenous antibiotics cefotaxime and amikacin were administered along with fluid supplementation. He was shifted to mother feed. The neonate was referred to the pediatric surgery department for further management.

Objective: In this retrospective single institution study, we investigated the clinicopathologic features and treatment characteristics of 90 patients with congenital corneal opacities (CCO) (117 eyes) who were 3 years and younger and treated at our hospital. Subject and Methods: We reviewed the clinical data of patients with CCO who presented for the first time for treatment at our hospital between January 1, 2017, and December 31, 2017. CCO were classified using the “STUMPED” (Sclerocornea, Tears in Descement’s membrane, Metabolic, Peters, Endothelial dystrophy and Dermoid) method and confirmed by pathological examination. ­Results: Seventy percent of the patients had unilateral CCO. Iridocorneal adhesions (61 eyes, 52.1%) and cataracts (22 eyes, 18.8%) were the 2 most common ocular abnormalities. Systemic abnormalities were present in 5 patients (5.6%), including growth retardation (4 patients) and congenital brain defects (1 patient). Eighty-five eyes (72.6%) underwent penetrating keratoplasty (PK), and lamellar keratoplasty (LK) was performed in 30 (25.6%) eyes. Forty-seven (95.9%) eyes with Peters anomaly and all 16 eyes with sclerocornea received PK, and all 24 eyes with dermoids were treated with LK. Conclusion: Our study demonstrates that CCO has varied manifestations in infants and young children in China. A thorough medical history, careful clinical examination, and the use of accessory examinations such as ultrasound biomicroscopy are critical for the accurate diagnosis and classification of CCO and to provide guidance on therapeutic choices.

Microphthalmia with brain and digital anomalies (MCOPS6, MIM# 607932) is an autosomal dominant disorder caused by loss-of-function variants or large deletions involving BMP4, which encodes bone morphogenetic protein 4, a member of the TGF-β protein superfamily. BMP4 has a number of roles in embryonic development including neurogenesis, lens induction, development of cartilage and bone, urogenital development, limb and digit patterning, hair follicle regeneration, as well as tooth formation. In addition to syndromic microphthalmia, BMP4 variants have been implicated in non-syndromic cleft lip with or without cleft palate and congenital healed cleft lip indicating different allelic presentations. MCOPS6 subjects may also lack some of the major phenotypic hallmarks of the disorder, including microphthalmia, indicating variable expressivity. As only a handful of individuals with MCOPS6 have been described, we review the clinical findings in previously reported cases with either deletions or loss-of-function variants in BMP4. We describe three new cases, including two subjects with novel deletions and one subject with a likely pathogenic de novo nonsense variant [c.1052C>G, p.(S351*)] in BMP4. One of the subjects had dual molecular diagnoses including a co-occurring microdeletion at 17q21.31 associated with Koolen de Vries syndrome, which has a partially overlapping disease phenotype. None of these individuals had clinically apparent microphthalmia or anopthalmia, which have been reported in a majority of previously described cases. One subject had exophthalmia and strabismus, while another had bilateral Peters anomaly and sclerocornea, thus expanding the phenotype associated with BMP4 loss-of-function variants.

Congenital corneal clouding often causes diagnostic dilemma; hence, detailed evaluation and timely intervention are required to decrease the morbidity. Various genetic, developmental, metabolic, and idiopathic causes of congenital corneal clouding include Peters anomaly, sclerocornea, birth trauma, congenital glaucoma, mucopolysaccharidosis, and dermoids. We report a case series of four neonates with congenital corneal clouding admitted in our neonatal intensive care unit, over 5 years. Two cases were of Peters anomaly, one each of primary congenital glaucoma and glaucoma secondary to congenital rubella.

When a newborn exhibits dermal aplasia on the face and neck, especially if there are ocular anomalies, further investigation is needed to determine if they have MiDAS (microphthalmia, dermal aplasia, and sclerocornea) or other syndromes with associated skin findings. It is essential to diagnose MiDAS syndrome early in life to allow for thorough workup to determine if there are any associated abnormalities in the child that require treatment. While the skin lesions of MiDAS syndrome heal spontaneously, other associated abnormalities require early intervention and can be life threatening.

Patient: Male, 11-month-old Final Diagnosis: Microphthalmos with massive retinal gliosis Symptoms: Microphthalmos with no useful vision, left eye Medication: — Clinical Procedure: Enucleation, left eye Specialty: Ophthalmology • Pathology Objective: Congenital defects/diseases Background: Massive retinal gliosis (MRG) is a rare benign intraocular tumor that results from the proliferation of well-differentiated glial cells in response to long-standing pathological processes, including glaucoma, trauma, chronic inflammation, vascular disorders, and congenital anomalies. This lesion is considered to be nonneoplastic and occurs ≥10 years after the predisposing insult. It usually affects children and can mimic other conditions, including uveal melanomas, vasoproliferative tumors of the retina, astrocytic hamartomas, and retinal hemangioblastomas. Case Report: We present a case of infant MRG with severe left eye microphthalmia. An 11-month-old boy was presented by his parents in the Oculoplastic Unit of a teaching university hospital with bilateral incomplete cryptophthalmos and small globes. An enucleation of the left globe was carried out to stimulate orbital bone growth and to improve the cosmetic outcome. The histopathological examination revealed a microphthalmic globe with sclerocornea and disorganized intraocular anterior segment structures. The retina was dysplastic with proliferating spindle-shaped glial cells showing fibrillar eosinophilic cytoplasm and filled most of the vitreous cavity. The glial origin of the cells was confirmed by the immunohistochemical markers (glial fibrillary acidic protein and synaptophysin), supporting the diagnosis of MRG. The optic nerve was markedly hypoplastic. Conclusions: MRG is a rare intraocular tumor that is clinically difficult to diagnose. A definite diagnosis can be made only on the basis of a histopathological examination and immunohistochemical markers.

Previously, we identified RAD21R450C from a peripheral sclerocornea pedigree. Injection of this rad21 variant mRNA into Xenopus laevis embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous rad21 variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in X. laevis embryos. In X. laevis embryos injected with rad21 mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21R450C variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development.

Sclerocornea is a rare congenital anomaly with clouding of the peripheral cornea that possibly extends up to the center of the cornea. Characteristically, a clear distinction (limbus) between sclera and cornea is lacking. Early surgical treatment is essential for preventing amblyopia, but penetrating keratoplasty in children carries a relatively high risk of complications. Especially for sclerocornea, penetrating keratoplasty has generally been reported to have a poor surgical outcome and a high risk of complications, including corneoscleral adhesions. Here, we report the 4-year follow-up on a child with sclerocornea, who was successfully operated on at the age of 3 months and had a favorable outcome. Our findings suggest that in some cases, penetrating keratoplasty may be an option to treat sclerocornea in young children., GMS Ophthalmology Cases; 10:Doc35

The concepts of pediatric keratoprosthesis (KPro) and more recently infant keratoprosthesis are relatively new. Our first case was performed in 2003..

Background. Sclerocornea is a rare congenital disorder characterized with the opacification of the cornea. Here, we report a nonconsanguineous Chinese family with multiple peripheral sclerocornea patients spanning across three generations inherited in an autosomal dominant manner. Methods. This is a retrospective case series of a peripheral sclerocornea pedigree. Comprehensive ophthalmic examinations were conducted and assessed on 14 pedigree members. Whole-exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from the family members. Functional tests were performed with these cell lines. Results. Six affected and eight unaffected members of a family with peripheral sclerocornea were examined. All affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were found significantly decreased in the affected members. Significant differences were also observed on the mean apex pachymetry between affected and unaffected subjects. These ophthalmic parameters did not resemble that of cornea plana. A RAD21C1348T variant was identified by whole-exome sequencing. Although this variant causes RAD21 R450C substitution at the separase cleavage site, cells from peripheral sclerocornea family members had no mitosis and ploidy defects. Conclusion. We report a family of peripheral sclerocornea with no association with cornea plana. A RAD21 variant was found cosegregating with peripheral sclerocornea. Our results suggest that RAD21 functions, other than its cell cycle and chromosome segregation regulations, could underline the pathogenesis of peripheral sclerocornea.

PURPOSE: To report the customized approach of patients with anophthalmia or microphthalmia with bespoke ocular prosthesis. METHODS: Retrospective analysis of case series. RESULTS: The study included cases with anophthalmia with upper eyelid deformity (one patient), microphthalmia and contralateral corectopia (one patient), microphthalmia with contralateral corneal graft (one patient), and congenital clinical anophthalmia with contralateral sclerocornea (one patient). Using techniques of embedded autologous hair and coating of adhesive pigment emulsion in the ocular prosthesis, the physical appearance of, respectively, an upper eyelid, corectopia, corneal graft, and sclerocornea was reproduced. CONCLUSION: Tailoring the ocular prosthesis to the distinct condition of the anophthalmic socket and contralateral eye adds to the success of rehabilitative prosthetic treatment of the patient.

International audience; GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype-phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

Sclerocornea is a cornea opacification disorder. Disorganized corneal stroma fibrils are observed in patients’ cornea. Previously we identified a RAD21C1348T variant that is associated with a peripheral sclerocornea pedigree. To explore whether this RAD21 variant can induce sclerocornea-related phenotype, and to investigate the possible mechanisms of such phenotype, the orthologous rad21 wild-type and variant mRNAs were injected into Xenopus laevis embryos and the developed eyes were subjected for histological examination. Transmission electron microscopy was applied for corneal stroma organization check. rad21 is highly expressed in the eye region during X. laevis development. Disrupted eye development was observed in the rad21 variant injected embryos. Disorganized corneal stroma and decreased diameters of collagen fibrils were observed in the rad21 variant injected X. laevis eyes. These eye defects can be rescued by overexpression of the wild-type rad21. Histological examination found stroma attracting center, a key structure in X. laevis corneal development, was impaired in rad21 variant injected embryos. Our results suggest a key role of RAD21 during corneal development. Our data indicates the RAD21R450C variant contributes to peripheral sclerocornea by disturbing collagen fibril organization in the corneal stroma.

BackgroundSclerocomea is a rare congenital disorder characterized with cornea opacification. We identified a heterozygous missense RAD21 variant in a non-cons anguineous Chinese family with multiple peripheral sclerocomea patients spanning across three generations inherited in an autosomal dominant manner.MethodsComprehensive ophthalmic examinations were conducted on all 14 members. Whole exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from all members. Cleavage of RAD21 protein was quantified in these cell lines.ResultsAll affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were significantly decreased in the affected members. Significant differences were also observed on mean apex pachymetry between affected and unaffected subjects. A RAD21C1348T variant was co-segregated with affected members. Both the wild-type allele and the missense variant were expressed at the mRNA level. This variant caused RAD21 R450C substitution at the separase cleavage site, which led to reduced RAD21 cleavage.ConclusionWe believe this is the first report of genetic variant in sclerocornea without other syndromes. Further work is needed to confirm the RAD21R450C variant with sclerocomea.

Patau syndrome when caused by attachment of an extra chromosome with chromosome 13 is called as full trisomy 13. It is caused by nondisjunction of chromosomes during meiosis. The extra chromosome disrupts normal development, causing multiple and complex organ defects. Children with trisomy 13 are born full term, but they rarely live more than a few days or weeks. Our patient was a 1-year-old female child who presented with various typical and atypical ocular and systemic findings of full trisomy 13. Her karyotyping showed the presence of an extra copy of chromosome 13. Anterior segment dysgenesis is known to occur with Patau's syndrome, but sclerocornea as a manifestation of full trisomy 13 has not been reported prior.

To determine the antiseptic efficacy of timely intraoperative iodine irrigation during cataract surgery. A total of 198 eyes of 99 cataract surgery patients were studied. The eyes were randomly assigned to treatment with or without timely intraoperative iodine irrigation of the surgical field with an iodine compound equivalent to 0.33 % povidone-iodine. In eyes in the timely intraoperative iodine irrigation group, the ocular surface was irrigated twice intraoperatively—before the initial incision and before insertion of the intraocular lens (IOL). The efficacy of the antiseptic treatment was evaluated by culture tests using scrapings of the surface of the sclerocornea and conjunctiva to the left of the incision and by broad-range real-time PCR for bacterial 16S ribosomal DNA using scrapings from the right side of the incision. Following intraoperative application of the iodine, bacteria were not detected in cultures of the samples. For the control eyes without timely iodine irrigation, cultures of samples from five and two eyes were positive before the initial incision and before IOL insertion, respectively. The bacterial DNA copy number before the initial incision was 1.7 ± 0.5 × 103, which was significantly lower than that of the control eyes (1.7 ± 0.6 × 104). For both groups of eyes, the bacterial DNA copy number was significantly lower before the IOL insertion depending on the time course. When the antiseptic effect of the iodine irrigation and time course on bacterial DNA copy number was analyzed using generalized mixed linear regression, both were found to be significantly effective. No significant intraoperative epithelial defect was observed. The postoperative corneal endothelial cell count did not differ significantly between the two groups of eyes. Timely iodine irrigation can serve as a simple and useful adjunctive disinfection step in cataract surgery.

Congenital cataracts are a significant cause of lifelong visual loss. They may be isolated or associated with microcornea, microphthalmia, anterior segment dysgenesis (ASD) and glaucoma, and there can be syndromic associations. Genetic diagnosis is challenging due to marked genetic heterogeneity. In this study, next‐generation sequencing (NGS) of 32 cataract‐associated genes was undertaken in 46 apparently nonsyndromic congenital cataract probands, around half sporadic and half familial cases. We identified pathogenic variants in 70% of cases, and over 68% of these were novel. In almost two‐thirds (20/33) of these cases, this resulted in new information about the diagnosis and/or inheritance pattern. This included identification of: new syndromic diagnoses due to NHS or BCOR mutations; complex ocular phenotypes due to PAX6 mutations; de novo autosomal‐dominant or X‐linked mutations in sporadic cases; and mutations in two separate cataract genes in one family. Variants were found in the crystallin and gap junction genes, including the first report of severe microphthalmia and sclerocornea associated with a novel GJA8 mutation. Mutations were also found in rarely reported genes including MAF, VIM, MIP, and BFSP1. Targeted NGS in presumed nonsyndromic congenital cataract patients provided significant diagnostic information in both familial and sporadic cases.

There are only few case reports of congenital anterior staphyloma, an extremely rare condition. We report a case of congenital anterior staphyloma presenting as corneal clouding. A preterm girl baby was noted at birth to have bilateral corneal opacity with left sided microcornea. Ophthalmological evaluation revealed anterior staphyloma in right eye &total leucomatous corneal opacity in left eye. Despite antiglaucoma treatment, right sided bupthalmos & corneal thinning worsened. Corneal transplant was done at 7 months of age & baby improved symptomatically.Congenital anterior staphyloma occurs due to developmental aberration or secondary to inflammation. There are various genetic, metabolic, developmental & idiopathic causes of congenital corneal clouding like congenital glaucoma, birth trauma, peters anomaly, dermoid tumors, sclerocornea, infectious/inflammatory processes, metabolic causes & excess prenatal maternal consumption of alcohol. Complete evaluation of congenital corneal clouding include slit lamp biomicroscopy, funduscopy, tonometry, gonioscopy, ultrasonography, photo screening, ultrasound biomicroscopy & CT scanning in selected cases. Treatment is primarily surgical followed by management of amblyopia & optical therapy. Early penetrating keratoplasty, primary combined trabeculotomy-trabeculectomy & corneal grafting are associated with a favorable visual outcome. Early identification of ophthalmological problems in infancy & prompt intervention is mandatory for conditions like congenital corneal clouding.

Purpose: To evaluate causes and management of congenital corneal opacities (CCO) diagnosed in a tertiary care eye center and to compare the data with a previous study at the same institution. Methods: Computerized medical records in all patients with congenital corneal opacities diagnosed in the Cornea Service at Wills Eye Hospital (Philadelphia, PA) between January 1, 2007, and December 31, 2015, were retrospectively reviewed. Children aged 12 years and younger at the first visit were included in the study. Patients’ demographics, ocular diagnosis, laterality, associated ocular abnormalities, other ocular surgery performed prior or subsequent to the first visit, and their treatment were extracted from the medical records. Results: A total of 77 eyes in 56 patients were examined. The mean age at presentation was 32.8 ± 44.2 months, with the mean follow-up period of 26.7 ± 30.1 months. The most frequent diagnosis was Peters anomaly (53.2%), followed by limbal dermoid (13.0%), aniridia with glaucoma and microphthalmos (6.5%), sclerocornea and congenital glaucoma (5.2%), idiopathic (3.9%), Axenfeld-Rieger anomaly and Hurler syndrome (2.6%), and microcornea (1.3%). Primary keratoplasty was performed in 26 eyes, with the outcome rate in the clear cornea of 76.0% during the follow-up. Conclusion: Peters anomaly is the most common cause of congenital corneal opacities encountered at our institution. Penetrating keratoplasty is the most frequent choice of corneal surgery to treat congenital corneal opacities. Additional interventions during penetrating keratoplasty were moderately positively correlated with graft failure. This study also shows the rates of some etiologies of that changed over the recent decades in our tertiary care Cornea Service. Although Peters anomaly remains the most common presenting reason for congenital corneal opacities, its rate appears to be increasing over the recent decade. Congenital corneal opacities due to birth trauma, which is one of the preventable causes, were observed in a previous study in our clinic; however, no new cases were noted in this study.

Purpose To describe 2 sporadic Mexican patients having congenital bilateral, total sclerocornea, aphakia, and microphthalmia associated with novel mutations in the FOXE3 gene. Methods Two affected individuals with congenital bilateral, total sclerocornea, aphakia, and microphthalmia underwent detailed examinations including slit-lamp examination, visual acuity, and intraocular pressure measurements. Ocular ultrasonography and ultrasound biomicroscopy were performed. Genomic DNA was isolated from blood leukocytes in each subject, and molecular analysis of the FOXE3 gene was performed. For cosegregation analysis, presumable pathogenic variants were tested by Sanger sequencing in parental DNA. Results Molecular screening of FOXE3 was performed in 2 cases with congenital bilateral, total sclerocornea, aphakia, and microphthalmia. In patient 1, genetic analysis demonstrated a novel homozygous c.291C>G (p.Ile97Met) FOXE3 pathogenic variant. In patient 2, compound heterozygosity for the novel c.387C>G (p.Phe129Leu) transversion and for the previously reported c.244A>G (p.Met82Val) transition, was recognized. Conclusions The sclerocornea-microphthalmia-aphakia complex is a severe malformative ocular phenotype resulting from mutations in the FOXE3 transcription factor. To date, patients from at least 14 families with this uncommon ocular disorder have been described. The identification of 2 novel pathogenic variants in our patients expands the mutational spectrum in FOXE3-related congenital eye disorders. In addition, we performed a review of the clinical and genotypic characteristics of all published patients carrying biallelic FOXE3 mutations.

International audience; Microphthalmia and anophthalmia (MA) are severe developmental eye anomalies, many of which are likely to have an underlying genetic cause. More than 30 genes have been described, each of which is responsible for a small percentage of these anomalies. Among these, is the FOXE3 gene, which was initially described in individuals with dominantly inherited anterior segment dysgenesis and, subsequently, associated with recessively inherited primary aphakia, sclerocornea and microphthalmia. In this work, we describe 8 individuals presenting with an MA phenotype. Among them, 7 are carrying biallelic recessive FOXE3 mutations and 2 of these have novel mutations: p.(Ala78Thr) and p.(Arg104Cys). The last of our patients is carrying in the heterozygous state the recessive p.(Arg90Leu) mutation in the FOXE3 gene. To further understand FOXE3 involvement in this wide spectrum of ocular anomalies with 2 different patterns of inheritance, we reviewed all individuals with ocular abnormalities described in the literature for which a FOXE3 mutation was identified. This review demonstrates that correlations exist between the mutation type, mode of inheritance and the phenotype severity. Furthermore, understanding the genetic basis of these conditions will contribute to overall understanding of eye development, improve the quality of care, genetic counseling and, in future, gene-based therapies.

To report on the use of endoscopic cyclophotocoagulation (ECP) to treat congenital glaucoma in a triple X female with microphthalmia, dermal aplasia, and sclerocornea (MIDAS) syndrome.The patient demonstrated linear streaks on the face and neck consistent with dermal aplasia. The corneas were scleralized with ectatic areas of corneal thinning, and the eyes were microphthalmic. Ultrasound biomicroscopy demonstrated congenital aphakia and iris stumps. The patient had elevated intraocular pressure (IOP) that responded to topical glaucoma therapy in the right but not the left eye. Intraoperative endoscopy of the posterior segment revealed multiple hypopigmented chorioretinal lacunae surrounding a pale, cupped optic nerve. ECP of the ciliary processes in the left eye led to marked improvement in IOP.Patients with MIDAS syndrome can develop congenital glaucoma secondary to angle dysgenesis. This is the first case report to demonstrate the safe and effective use of ECP to treat elevated IOP in a patient with MIDAS.

Our objective is to evaluate the literature regarding selected genetic diseases of the cornea, including megalocornea, keratoglobus, keratoconus, cystinosis, the mucopolysaccharidoses, sclerocornea, Peters' anomaly, familial dysautonomia, and various corneal dystrophies. The transparency of the cornea is a consequence of uniformity in both size and spacing of the collagen lamellae. The cornea's clarity depends on a delicate biochemical and structural balance; consequently, genetic disorders that disrupt either its metabolic or anatomic function can cause opacity and vision loss. Many childhood corneal diseases have a genetic etiology and are associated with known syndromes. Each disorder has unique associated set of possible complications. Prognosis often depends on the extent of opacity and disorganization of the anterior segment. Corneal transplantation has been performed for these disorders with variable success.

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions.

Anterior segment development involves important contributions from neural crest cells as well as surface ectoderm. Transcription factors and other genetic influences orchestrate proper morphogenesis. Several forms of anterior segment dysgenesis, such as sclerocornea and Peters anomaly, lead to corneal opacity. However, this traditional terminology allows neither genotype–phenotype correlations nor prediction of outcomes following surgical intervention. A descriptive classification is presented as more valuable alternative. Corneal dystrophies, epibulbar choristomas, peripheral sclerocornea, and CYP1B1 cytopathy are discussed as forms of primary neonatal corneal opacification. Secondary corneal opacification can be congenital, due to kerato-irido-lenticular or irido-trabecular dysgenesis, or acquired following infection, trauma, or metabolic disease. Peters anomaly, aniridia, and Axenfeld-Rieger syndrome are discussed separately. Finally, congenital anomalies of corneal size—microcornea and megalocornea—and shape—cornea plana and keratoglobus—are reviewed.

Background: Sclerocornea, a congenital corneal pathology characterized by bilateral scleralization of the cornea, which can be found in few cases with posterior fossa malformationshemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe (PHACES) syndrome. Presence of vascularization in peripheral cornea and smaller diameter of recipient cornea correlate to poor outcome of penetrating keratoplasty (PKP) in sclerocornea. Here we report a method to preserve limbus during PKP for small, irregular, and scleralized cornea. Methods: A 12-year-old boy with multiple congenital anomalies diagnosed as PHACES syndrome suffered from bilateral total sclerocornea and poor visual acuity. Due to the fact that the left eye cornea was small (6.5 mm × 10 mm), lamellar dissection and posterior recession of inferior limbus was first performed and followed by a 6 mm trephination and PKP with a 6.5 mm graft for left eye. At the same time, lens aspiration and release of peripheral anterior synechia were performed. Results: After 6 years of follow-up, the cornea remained clear, and there has been no sign of inflammation and conjunctivalization. The patient maintained useful vision of 20/400 in left eye. Conclusion: The stabilization of corneal surface is possible after PKP for sclerocornea if the limbus can be preserved during the operation, and epithelium can remain corneal in phenotype preventing pannas growth.

Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases. The two additional cases presented in this report expand the phenotypic spectrum of 8q21.11 microdeletions to include Peters anomaly (seen in both patients) and persistent primary dentition (seen in one patient with a larger deletion). The two novel deletions include the ZFHX4 and PEX2 genes, which were also affected in all three previous cases involving ocular anomalies. Screening of the remaining alleles of ZFHX4 and PEX2 did not identify any additional likely pathogenic variants in either patient, suggesting a dominant mechanism (haploinsufficiency) for the identified deletion. This report provides further insight into the phenotypes associated with 8q21.11 deletions and, for the first time, reports Peters anomaly as an additional ocular feature; screening for copy number variations of the 8q21.11 region should be considered in patients with Peters anomaly and related syndromic features. © 2016 Wiley Periodicals, Inc.

PURPOSE We aim to analyze the results of Boston type 1 keratoprosthesis from the Indian subcontinent, with particular emphasis on patient education and perioperative care. DESIGN Retrospective interventional case series. METHODS This was a retrospective study of patients operated on for Boston type 1 keratoprosthesis between January 2008 and April 2011. RESULTS Of 20 patients who underwent surgery, the indications included silicone oil-induced keratopathy (8 eyes; 40%), chemical injury (7 eyes; 35%), repeated graft failures (3 eyes, 15%), and 2 pediatric eyes (10%)-1 sclerocornea and 1 congenital anterior staphyloma. The mean follow-up was 21.8 months ranging from 6 to 45 months. Best corrected postoperative visual acuity was noted to be greater than 20/200 in 16 (80%) of 20 eyes. Anatomic integrity was maintained in 18 eyes (90%). Repeated corneal melt necessitated removal of the prosthesis with corneal transplant in 2 eyes. There was no infection or endophthalmitis in any of the 20 eyes. CONCLUSIONS The good anatomic and functional results, with no postoperative infection in our experience with Boston keratoprosthesis over a 3-year period, are encouraging. Strict inclusion criteria and ensuring good patient compliance are important factors in determining good results with a low risk of infection in a tropical developing country.

The Goldenhar anomaly (GA) is a heterogeneous field defect of uncertain cause and wide variability of expression, characterized by facial phenotypes, usually asymmetric and unilateral, accompanied by various combinations and gradations of cardiac, skeletal, renal, and central nervous system defects. We report the pathologic findings in a 5-month-old boy with GA, tracheal stenosis, and left unilateral sclerocornea. To the best of our knowledge this is the first description of sclerocornea in a patient with GA.

Purpose To compare a transconjunctival single-plane sclerocorneal incision with 2 tiny conjunctival cuts at both ends and a clear corneal incision (CCI) in cataract surgery. Setting Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. Methods Patients having routine cataract surgery were randomly divided into 2 groups based on incision type; that is, transconjunctival single-plane sclerocorneal or CCI. The incidence of intraoperative ballooning of the conjunctiva (chemosis) and the percentage of eyes that required stromal hydration to securely close the wound in each group were recorded and compared. Results Each group comprised 61 eyes (61 patients). No eye in the transconjunctival sclerocorneal group and 6 eyes (9.8%) in the CCI group developed intraoperative conjunctival chemosis ( P = .027, Fisher exact probability test). Corneal stromal hydration was required in 2 eyes (3.3%) and 15 eyes (24.6%), respectively ( P = .001). Conclusion The transconjunctival single-plane sclerocorneal incision was effective and combined the merits of CCI incisions and sclerocorneal incisions. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop normally. In humans, autosomal dominant and recessive mutations in FOXE3 have been associated with variable phenotypes including anterior segment anomalies, cataract and microphthalmia. We undertook sequencing of FOXE3 in 116 probands with a spectrum of ocular defects ranging from anterior segment dysgenesis and cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found in four of 26 probands affected with bilateral microphthalmia (15% of all bilateral microphthalmia and 100% of consanguineous families with this phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or corneal defects; no other associated systemic anomalies were observed in FOXE3-positive families. The previously reported c.720C>A (p.C240X) nonsense mutation was identified in two additional families in our sample and therefore appears to be recurrent, now reported in three independent microphthalmia families of varied ethnic backgrounds. Several missense variants were identified at varying frequencies in patient and control groups with some apparently being race-specific, which underscores the importance of utilizing race/ethnicity-matched control populations in evaluating the relevance of genetic screening results. In conclusion, FOXE3 mutations represent an important cause of nonsyndromic autosomal recessive bilateral microphthalmia.

Congenital clinical anophthalmos and blind microphthalmos are extremely rare conditions, with a prevalence rate of 1–20/100,000 newborns. Distribution of the conditions is approximately equal between males and females. Unilateral anophthalmos is encountered almost twice as frequently as bilateral anophthalmos. Microphthalmos is the least-common reason why patients present for surgery. With a single exception, the family histories were not positive for the conditions. The course of pregnancy itself was routinely unexceptional. Consanguinity and pathological chromosomal abnormalities point to the possible role of genetic factors, which are increasingly becoming the focus for research. As expected, obstetric delivery was not a determinant of the clinical condition. Comprehensive evaluation of each case requires a thorough ophthalmological examination supplemented by assessment by an experienced pediatrician. Associated systemic findings were more numerous in patients with anophthalmos (50%) than in those with microphthalmos (17.6%). There was no difference in the rate of developmental anomalies in unilateral and bilateral anophthalmos. Typically, the pathology is characterized by Goldenhar syndrome and clefting. Magnetic resonance imaging (MRI) is generally necessary to detect developmental cerebral anomalies. Nasolacrimal duct pathology was present in about 75% of the affected children. Canalicular stenoses were the most common finding. Twenty-five percent of patients with unilateral microphthalmos and 50% of patients with unilateral anophthalmos had anomalies in the fellow eye, chiefly in the form of coloboma, dermoid, sclerocornea, and glaucoma. On account of this pathology in a single eye, 2 (12.5%) of the patients with unilateral microphthalmos and 13 (34.2%) of the patients with unilateral anophthalmos, as well as all 20 patients with bilateral anophthalmos, were classified as legally blind. Therefore, the overall blindness rate was 17.6% in microphthalmos and 3.4 times higher (56.9%) in anophthalmos.

We report the case of a now 6-year-old girl who was born with different abnormalities in each eye. The right eye showed a total sclerocornea. At the age of 4 years we performed a perforating keratoplasty. On the left eye a large staphyloma developed. The staphyloma was excised and a cornea with a scleral rim was fixed in. This transplant became cloudy under a conjunctival flap and blepharoplasty. In addition to the clinical follow-up, histological and immun-histochemical examinations of the corneas were carried out.

Here we report on a 1-year-old Japanese girl with psychomotor retardation, bilateral congenital corneal opacity and bilateral postaxial polysyndactyly of the feet. Although she had a normal female karyotype, our in-house bacterial artificial chromosome (BAC)-based array-CGH analysis successfully detected at least a 2.7-Mb heterozygous deletion at 14q22.1-q22.3 harboring 18 protein-coding genes. Among the genes, BMP4 was a candidate for the gene causing the abnormalities of both the eye and digits. It was previously reported that the BMP family was correlated with the morphogenesis of digits and ocular development, and Bmp4 heterozygous null mice revealed skeletal abnormalities including polydactyly and ocular anterior segment abnormalities. Patients with a deletion including BMP4 also hadabnormalities of the eye and digits. These previous reports support that a haplo-insufficiency of the BMP4 gene likely caused the congenital ocular and digit abnormalities. Moreover, among the other genes contained in the deletion, GMFB is a candidate for the gene responsible for the psychomotor retardation.

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia, left microphthalmia and sclerocornea. In this study, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia.

To describe the histopathology of the cornea in microphthalmia with linear streaks (MLS) syndrome.Two patients with MLS syndrome underwent penetrating keratoplasty. This study describes the histopathology and investigates immunophenotype of the corneal extracellular matrix by using keratan sulfate and collagen type III antibodies.Clinical examination revealed bilateral sclerocornea and characteristic skin changes. By light microscopy, central corneal stroma in both patients showed vascularization and irregular thick collagen lamellae typical of sclerocornea. In addition, corneal thinning, anterior synechiae, and the absence of the Descemet membrane were noted, which was suggestive of Peters anomaly. Diffuse and intense anti-keratan sulfate staining and minimal anti-collagen type III stromal staining were seen in both corneal buttons.The cornea in MLS may clinically resemble sclerocornea. Histologic features resemble those previously described in sclerocornea and also seen in anterior segment dysgeneses. Keratan sulfate and collagen type III labeling suggests that the corneal extracellular matrix resembled cornea and not sclera.

We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.

A newborn presented to genetics with complex skeletal abnormalities, joint contractures, and bilateral corneal clouding with sclerocornea. The patient survived for 8 months before succumbing to respiratory failure. Exome sequencing revealed a compound heterozygous mutation in theB3GALT6gene. Mutations in this gene have been associated with both Ehlers- Danlos syndrome, progeroid type 2 and spondyloepimetaphyseal dysplasia with joint laxity type 1. These diagnoses encompass the skeletal and joint findings. Our patient expands the phenotype of these diagnoses, as anterior segment eye anomalies have not been described with either syndrome, and he is much more profoundly affected. Interestingly, our patient fits the description of a rare genetic disease referred to as Al-Gazali syndrome, for which the genetic cause is unknown.

Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553-559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2010] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2. © 2014 Wiley Periodicals, Inc. ispartof: American Journal of Medical Genetics A vol:164 issue:5 pages:1170-1174 ispartof: location:United States status: published

International audience; BACKGROUND: Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death. METHODS: We characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed. RESULTS: Two terminal Xp deletions of >=11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of >=3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient. CONCLUSION: Our findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes.

Editor—Microphthalmia with linear skin defects (MLS) is a clinically complex and highly variable phenotype in XX subjects and has been considered to be at least partially determined by three features: the pattern of X chromosome inactivation; the extent of the Xp22.3 segmental monosomy; and the nature of the chromosomal anomaly (deletion or translocation).The recurring features of microphthalmia with linear skin defects, generally restricted to the face and neck in all the early reported cases, led to its designation as the MLS syndrome. The consistent association of these two manifestations with Xp22.3 segmental monosomy suggests that MLS is a contiguous gene syndrome.1 2However, the phenotype may be complicated by additional abnormalities which include sclerocornea, chorioretinal abnormalities, agenesis of the corpus callosum, hydrocephalus, infantile seizures, mental retardation, and congenital heart defects. To date, around two dozen cases of MLS syndrome (including our case) have been published and in approximately half (including our case), the Xp22.3 disruption has resulted from a terminal deletion.3-10 In the remaining cases, Xp22.3 segmental monosomy is a consequence of X;Y8 11-13 or X;autosome translocations.14-18 In all cases, there is monosomy for over 10 megabase pairs and comparison with patients harbouring smaller deletions has defined a ∼570 kb interval that must contain the gene(s) giving rise to the diagnostic clinical features of the disorder, including microphthalmia, sclerocornea, and linear skin defects. Subsequent and ongoing investigations have led to the identification and characterisation of three genes from this minimal region as well as the precise mapping of a number of expressed sequence tags (ESTs). However, it is still currently unknown which gene(s) are responsible for this unique combination of features. Wapenaar et al 19 20 used cell lines from 10 MLS cases with deletions and translocations involving the Xp22 region to investigate the minimal …

Purpose To report the preliminary results of a surgical technique for transplantation of posterior corneal tissue through a sclerocorneal pocket incision for corneal endothelial disorders. Design Retrospective, noncomparative, interventional cases series. Participants and intervention In seven sighted human eyes, a deep stromal pocket was created across the cornea through a 9.0-mm superior scleral incision. A 7.0- or 7.5-mm diameter, posterior lamellar disc was excised and replaced by a ‘same size' donor posterior disc, without suture fixation. The scleral incision was sutured. Main outcome measures Intra- and postoperative complications, best spectacle-corrected visual acuity, keratometry, topography, biomicroscopy, pachymetry, and endothelial cell density were evaluated. Results Six to 12 months after surgery, all transplants were clear and in position. Best spectacle-corrected visual acuity was limited by preexisting maculopathies in two eyes and varied from 20/80 to 20/20. Postoperative astigmatism averaged 1.54 diopters (D; standard deviation [SD] ± 0.81 D), pachymetry averaged 0.49 mm (SD ± 0.09 mm), and postoperative endothelial cell density averaged 2520 cells/mm 2 (SD ± 340 cells/mm 2 ). In one eye, a microperforation occurred during stromal pocket dissection so that the procedure was converted into a penetrating keratoplasty. Conclusions Posterior lamellar keratoplasty through a sclerocorneal pocket incision is a feasible surgical approach to manage corneal endothelial disorders.

Objetivo: Descrever os casos de dois irmãos com diagnóstico de córnea plana congênita bilateral e alta hipermetropia, uma vez que não temos, no Brasil, conhecimento de referências anteriores sobre famílias afetadas por tal entidade. Relato dos casos: Dois irmãos com grave aplanamento corneal, "esclerização" limbar, opacidade estromal central, achatamento da câmara anterior, elevada hipermetropia e pseudo-ptose. Discussão: Córnea plana congênita é uma entidade extremamente rara, caracterizada pelo achatamento anormal da curvatura corneal. Discute-se os possíveis tipos de herança, uma vez que cada um produz apresentação clínica característica desta entidade que, neste caso, ao lado da distribuição familiar, corrobora com o diagnóstico de córnea plana congênita com herança autossômica recessiva. Chama-se a atenção para o erro de refração e prevenção do glaucoma, cuja inci-dência está aumentada nestes casos.Purpose: To report two cases of bilateral cornea plana with high hypermetropia. Case report: Two members of the same family showed se-vere corneal flattening, limbal "scleralization". The sha-lowness of the anterior chamber, deep stromal corneal opacities and upper lid with ptotic appearance besides the familial distribuition are supposed to agree with the documented description of the recessive variety of cornea plana. Discussion: The management of the cornea plana is discussed.

· Background: To detect the associated anomalies in patients with Axenfeld-Rieger syndrome is clinically important, because early treatment for such anomalies is crucial to both visual and systemic development. This study was conducted to clarify the associated anomalies in the syndrome. · Methods: We evaluated 21 patients with Axenfeld-Rieger syndrome encountered at Nagoya City University Hospital over a 16-year period. Patients who presented with a prominent Schwalbe’s line accompanying the iris strands were diagnosed as having Axenfeld-Rieger syndrome. · Results: The series consisted of 9 males and 12 females, ranging in age from 1 month to 41 years, mean 15.4±12.7 (SD) years. The syndrome was bilateral in 17 cases and unilateral in 4 cases. Hypoplasia of the iris was observed in 10 eyes of 6 patients. The associated ocular anomalies included sclerocornea in 6 eyes of 3 patients, developmental glaucoma in 5 eyes of 3 patients, persistent pupillary membrane in 4 eyes of 2 patients, microphthalmos in 3 eyes of 2 patients, and typical iris coloboma in 1 eye. Of 10 eyes with hypoplasia of the iris, 5 exhibited glaucoma. The accompanying systemic anomalies included 9 cases of dental anomalies, 5 of facial anomalies, and 3 of Alagille syndrome. · Conclusions: All of the associated ocular and systemic anomalies appeared to arise from the maldevelopment of the neural crest cells. Patients with Axenfeld-Rieger syndrome should therefore be examined for the presence of anomalies in the tissues of neural crest origin. Patients with hypoplasia of the iris should be checked for glaucoma.

We report on a male child with "apple peel" atresia, associated with microcephaly, with subsequent hydrocephalus, short stature, moderate global developmental delay and ocular abnormalities. A similar phenotype was previously reported by Stromme et al. in 1993 in female siblings, and this description of another affected individual provides further evidence for this being a distinct syndromic entity.

AIM—To describe the prognosis and complications of corneoscleral transplantation in the management of end stage eye disease. METHODS—A case series is presented of 23 patients who have undergone corneoscleral transplantation (⩾11 mm). Patients were examined for visual acuity, intraocular pressure, recurrence of disease process, epithelialisation of the graft, signs of rejection, and other potential complications. RESULTS—14 patients retained their eye, with six maintaining a clear graft. Vision ranged from 6/30 to no perception of light. 13 patients developed glaucoma (range 25-69 mm Hg), with six patients requiring surgical intervention. 12 patients required tarsorrhaphy to promote epithelialisation. Only two grafts resulted in typical rejection. CONCLUSIONS—The technique of corneoscleral transplantation can salvage otherwise end stage eye disease, but the results are poor with respect to maintenance of vision. These patients need careful follow up because of potential complications of glaucoma, epithelial defects, rejection, and recurrence of disease. Keywords: corneoscleral graft; end stage corneal disease; sclerokeratoplasty

Hautdefekte in segmentaler Anordnung und Mikrophthalmus sind Leitsymptome des kongenitalen Varizellensyndroms. Ein genetisch bedingtes Krankheitsbild, das MIDAS-Syndrom (MI=Mikrophthalmus; DA=dermal aplasia; S=Sklerokornea), hat eine ahnliche klinische Symptomatik. Dieser Erkrankung liegt eine terminale Deletion des kurzen Arms des X-Chromosoms im Bereich Xp 22.3 zugrunde. Diskussion: Wir stellen das Krankheitsbild anhand eines Falls vor und diskutieren weitere Differentialdiagnosen wie das Aicardi- und das Goltz-Gorlin-Syndrom.