RESUMEN

PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Asunto(s)

Enfermedades de la Córnea , Opacidad de la Córnea , Niño , Humanos , Estudios Retrospectivos , Células Endoteliales , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Opacidad de la Córnea/cirugía , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/genética , Fenotipo , Variación Biológica Poblacional , Citocromo P-450 CYP1B1/genética

RESUMEN

PURPOSE: The aim of this study was to report a case of corneal plana-like phenotype with bilateral peripheral scleralization associated with a PITX2 pathogenic variant. METHODS: Clinical findings were obtained by ophthalmologic examination. Molecular diagnosis was performed by whole-exome sequencing in the patient and his parents. RESULTS: A 12-month-old male patient present with bilateral peripheral corneal scleralization, corneal plana-like phenotype, and iris hypoplasia. The genetic analysis revealed a de novo PITX2 pathogenic variant (c.323G>A, p.R108H). CONCLUSIONS: PITX2 c.323G>A (p.R108H) can be associated with a unique corneal plana-like phenotype with peripheral scleralization, and thus, PITX2 should be targeted in genetic testing of this specific phenotype.

Asunto(s)

Enfermedades de la Córnea , Proteínas de Homeodominio , Humanos , Masculino , Enfermedades de la Córnea/patología , Proteínas de Homeodominio/genética , Mutación , Linaje , Fenotipo , Factores de Transcripción/genética , Lactante , Proteína del Homeodomínio PITX2

RESUMEN

PURPOSE: Ocular surface lipodermoids with corneal involvement may require surgical intervention; if deep, ocular surface reconstruction with lamellar corneal tissue or amniotic membrane may be needed. We describe a staged technique using autologous ipsilateral simple limbal epithelial transplantation. METHODS: After verifying sparing of Descemet membrane, the conjunctival portion of the lipodermoid was debulked in the first stage. Six weeks later, the corneal portion was excised, followed by autologous ipsilateral simple limbal epithelial transplantation to promote rapid reepithelialization of the residual stromal bed. Temporary tarsorrhaphy was used for patient comfort and to expedite ocular surface healing. RESULTS: Three eyes of 3 children with grade III large ocular surface lipodermoids that encroached the visual axis and hindered proper eyelid closure underwent surgery without complications. In all cases, the visual axis was cleared and eyelid closure was improved. At the last follow-up (mean 35.7 months, median 36.0 months), the bed of the original dermoid showed minimal haze in 1 case, while 2 eyes developed small pseudopterygium; best spectacle-corrected visual acuity improved from 20/200 to 20/70 in the first case, from fix and follow to 20/50 in the second case, and remained fix and follow in the last case, but this child had congenital hydrocephalus with severe developmental delay. CONCLUSIONS: This surgical technique is a promising option for children with grade III large ocular surface lipodermoids given its effectiveness in clearing the visual axis and in improving eyelid closure. Moreover, it does not require lamellar corneal transplantation or intervention to the fellow eye.

Asunto(s)

Enfermedades de la Córnea , Trasplante de Córnea , Epitelio Corneal , Quemaduras Oculares , Limbo de la Córnea , Humanos , Niño , Agudeza Visual , Córnea/cirugía , Enfermedades de la Córnea/cirugía , Trasplante de Córnea/métodos , Trasplante Autólogo , Quemaduras Oculares/cirugía

RESUMEN

PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

Asunto(s)

Opacidad de la Córnea , Perforación Corneal , Síndrome de DiGeorge , Anomalías del Ojo , Humanos , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Opacidad de la Córnea/congénito , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Anomalías del Ojo/diagnóstico por imagen , Anomalías del Ojo/genética , Estudios Retrospectivos

RESUMEN

PURPOSE: Peters-plus syndrome is a rare, autosomal recessive congenital disorder of glycosylation caused by mutations in the gene B3GLCT. A detailed description of the ocular findings is currently lacking in the scientific literature. We report a case series of Peters-plus syndrome with deep ocular phenotyping using anterior segment optical coherence tomography and ultrasound biomicroscopy. Where available, we describe the histology of host corneal buttons. METHODS: A retrospective chart review of patients with Peters-plus syndrome was conducted under the care of the senior author between January 2000 and June 2019. Demographic and clinical data including ocular and systemic features, ophthalmic imaging, and molecular diagnostic reports were collected. RESULTS: Four cases of Peters-plus syndrome were identified. Three patients were male and 1 was female. Five of the 8 eyes had an avascular paracentral ring opacity with relative central clearing. The paracentral opacity is due to iridocorneal adhesion and the relative central clearing associated with posterior stromal thinning. One eye had persistent fetal vasculature and microphthalmia, which has not previously been reported. One eye from each of 2 patients had a significantly different phenotype with a large vascularized central corneal opacity. CONCLUSIONS: The most common ocular phenotype seen in Peters-plus syndrome is an avascular paracentral ring opacity with relative central clearing. A different phenotype with a large vascularized corneal opacity may also be observed.

Asunto(s)

Segmento Anterior del Ojo/anomalías , Labio Leporino/genética , Córnea/anomalías , ADN/genética , Galactosiltransferasas/genética , Glucosiltransferasas/genética , Trastornos del Crecimiento/genética , Deformidades Congénitas de las Extremidades/genética , Microscopía Acústica/métodos , Tomografía de Coherencia Óptica/métodos , Segmento Anterior del Ojo/diagnóstico por imagen , Labio Leporino/diagnóstico , Análisis Mutacional de ADN , Femenino , Galactosiltransferasas/metabolismo , Glucosiltransferasas/metabolismo , Trastornos del Crecimiento/diagnóstico , Humanos , Lactante , Recién Nacido , Deformidades Congénitas de las Extremidades/diagnóstico , Masculino , Fenotipo , Estudios Retrospectivos

RESUMEN

PURPOSE: Neurotrophic keratopathy (NK) produces persistent epithelial erosion which is hard to treat effectively. Recently, corneal neurotization surgery has produced reinnervation of the cornea with resolving neurotrophic keratopathy. We hypothesized that the generation of corneal epithelial nerves after neurotization surgery would not only restore the integrity of corneal epithelium but also produce a change in the configuration of the palisades of Vogt (POV), which houses the corneal epithelial stem cells. METHODS: We assessed a patient with unilateral congenital corneal anesthesia with optical coherence tomography pre-neurotization and post-neurotization. RESULTS: Over the course of 2 years, the patient gained corneal epithelial sensation and corneal and limbal epithelium was restored to normal thickness with corresponding changes in the POV. CONCLUSIONS: The intimate relationship between epithelium and sensory nerves of the cornea has been well documented; however, changes in the corneal epithelial stem cell niche in conjunction with development of innervation have not previously been reported. Considering the architecture of the corneal nerves in conjunction with the architecture of the POV may assist in developing treatments that can support the regeneration and maintenance of epithelium during nerve regeneration.

Asunto(s)

Córnea/inervación , Enfermedades de la Córnea/cirugía , Regeneración Nerviosa/fisiología , Transferencia de Nervios/métodos , Sensación/fisiología , Adulto , Córnea/fisiopatología , Enfermedades de la Córnea/fisiopatología , Epitelio Corneal/patología , Humanos , Masculino , Microscopía Confocal , Tomografía de Coherencia Óptica

RESUMEN

PURPOSE: Mycoplasma pneumoniae is a common cause of pediatric respiratory infections, with a quarter having extrapulmonary complications, most commonly a mucocutaneous eruption involving the ocular surface. A detailed description of the ophthalmic manifestations in Mycoplasma-induced rash and mucositis (MIRM) is currently lacking in the scientific literature. METHODS: This is a retrospective chart review of consecutive cases of MIRM at a tertiary referral children's hospital between October 1 and December 1, 2018, with up to 2 months of follow-up. Main outcomes and measures were demographic information, clinical examination findings including visual acuity, detailed anterior segment findings, and course of both ophthalmic and systemic disease. RESULTS: Five patients were included. Age range was 8 to 17 years (mean age 11.9 years, median 11 years), with a strong male preponderance (4:1). All patients had inflammatory conjunctivitis. One patient had recurrent conjunctival pseudomembrane formation, whereas 2 patients had lid margin and conjunctival ulceration. No cases had corneal involvement and visual outcomes were excellent. CONCLUSIONS: MIRM is associated with ocular involvement in almost all cases. Although this is generally mild, conjunctival epithelial defects and pseudomembrane formation can occur. We recommend that pediatric ophthalmologists follow children who are hospitalized with MIRM as closely as they would those diagnosed with other mucocutaneous syndromes, such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Asunto(s)

Conjuntiva/patología , Córnea/patología , Exantema/diagnóstico , Infecciones Bacterianas del Ojo/diagnóstico , Mucositis/diagnóstico , Infecciones por Mycoplasma/diagnóstico , Mycoplasma pneumoniae/aislamiento & purificación , Adolescente , Niño , Exantema/microbiología , Infecciones Bacterianas del Ojo/microbiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mucositis/microbiología , Infecciones por Mycoplasma/microbiología , Estudios Retrospectivos , Agudeza Visual

RESUMEN

Reports of systemic associations in patients with Isolated Sagittal Synostosis (ISS) are sparse. Craniofacial surgeons, and other providers, should be aware that a significant proportion of patients with ISS may have syndromic or systemic involvement. This study investigates the incidence of systemic disease and syndromic diagnosis in a cohort of patients presenting with ISS (ie, patients with sagittal synostosis without other sutural involvement). METHODS: This study consists of a retrospective review of patients diagnosed with ISS between 2007 and 2017 at a single institution. Patients were divided according to onset (early <1 year, late >1 year) of ISS. Patient notes were examined for congenital anomalies, systemic conditions, and molecular testing. Only patients with isolated sagittal fusion-meaning, patients with sagittal synostosis and no other sutural involvement-were included. RESULTS: Three hundred seventy-seven patients met the inclusion criteria: systemic conditions were identified in 188/377 (50%) of them. One hundred sixty-one patients with early onset (Group A), and 216 patients with late onset ISS (Group B) were identified. Systemic involvement was identified in 38% of Group A and 60% of Group B, which was statistically significant (P < 0.001). Forty-eight of 377 (13%) of patients had a syndromic diagnosis, and 79% of these were confirmed via genetic testing. Thirty-five percent of patients were diagnosed with central nervous system anomalies and 16% had craniofacial anomalies. CONCLUSIONS: Nearly 50% of the patients initially diagnosed with ISS were found to have some form of systemic involvement. This supports affording full pediatric and genetic evaluation with molecular testing to these children.

RESUMEN

PURPOSE: To describe the clinical signs of Descemet membrane (DM) detachment due to forceps-related birth injury and its subsequent management using optical coherence tomography. METHODS: Case report. RESULTS: A 3-day-old term infant presented with left eye corneal clouding and a definitive history of traumatic forceps-assisted delivery. Despite topical therapy, corneal clouding persisted, necessitating an examination under anesthesia using ultrasound and handheld optical coherence tomography. This revealed not only a tear in DM but also a large detachment. Injection of air alone failed to achieve apposition of DM to the posterior stroma. Apposition was achieved only after penetration of the overlying cornea with the needle of a 10-0 nylon suture and release of clear viscous fluid. The cornea cleared within the first week and continued in the months to follow. CONCLUSIONS: Prolonged corneal edema should alert the physician to probable DM detachment after forceps-related birth injury. Injecting air alone may not be sufficient to reattach the detached DM.

Asunto(s)

Traumatismos del Nacimiento/cirugía , Edema Corneal/cirugía , Opacidad de la Córnea/cirugía , Lámina Limitante Posterior/lesiones , Lesiones Oculares/cirugía , Forceps Obstétrico/efectos adversos , Traumatismos del Nacimiento/diagnóstico por imagen , Traumatismos del Nacimiento/etiología , Edema Corneal/diagnóstico por imagen , Edema Corneal/etiología , Opacidad de la Córnea/diagnóstico por imagen , Opacidad de la Córnea/etiología , Lámina Limitante Posterior/diagnóstico por imagen , Lesiones Oculares/diagnóstico por imagen , Lesiones Oculares/etiología , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Procedimientos Quirúrgicos Oftalmológicos , Tomografía de Coherencia Óptica

RESUMEN

PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.

Asunto(s)

Edema Corneal/tratamiento farmacológico , Proteínas del Complejo de Cadena de Transporte de Electrón/uso terapéutico , Endotelio Corneal/efectos de los fármacos , Distrofia Endotelial de Fuchs/tratamiento farmacológico , Síndrome de Kearns-Sayre/tratamiento farmacológico , Ubiquinona/análogos & derivados , Niño , Preescolar , Edema Corneal/diagnóstico , Endotelio Corneal/patología , Humanos , Síndrome de Kearns-Sayre/diagnóstico , Masculino , Soluciones Oftálmicas , Ubiquinona/uso terapéutico , Agudeza Visual/efectos de los fármacos

RESUMEN

As our understanding of phenotype has improved with improving anterior segment imaging, it has become increasingly clear that the early genotype-phenotype correlations were largely misled by inaccurate phenotyping. Using a novel classification, congenital or neonatal corneal opacification can be considered to be primary or secondary. Secondary corneal disease may be developmental or acquired. Genetic analysis using this phenotypic classification becomes easier to navigate. Primary corneal disease includes endothelial dystrophies, corneal dermoids, cornea plana, and CYP1B1 cytopathy. Genotyping for all these conditions is reasonably advanced. Secondary developmental corneal disease includes entities that are the least well understood genotypically. These are kerato-irido-lenticular dysgenesis (also known as Peters anomaly, types 1 and 2). The genotyping literature of these conditions is littered with confusion. Iridocorneal adhesions (Peters anomaly 1) are often avascular, whereas keratolenticular adhesions (Peters anomaly 2) are usually vascularized. Children with a known molecular diagnosis can have iridocorneal adhesion in one eye and keratolenticular adhesion in the other eye. This further supports the notion that Peters anomaly 1 or 2 is a sign and not a diagnosis. Further types of kerato-irido-lenticular dysgenesis are those in which the lens fails to form or forms and then degenerates. Genotyping in these cases has been somewhat more fruitful but, as always, not comprehensive. If the lens fails to form or forms partially, the gene involved is FOXE3, which is a lens gene. Not surprisingly, if the lens forms partially or fails to form, this has an effect on the vitreous and the drainage angle. These cases are often associated with severe glaucoma. Other secondary developmental corneal diseases may include Axenfeld-Rieger syndrome, Aniridia, and primary congenital glaucoma, all of which have specific genotypic characterization. Other secondary causes are acquired and include infection, trauma, and metabolic disorders.

Asunto(s)

Segmento Anterior del Ojo/anomalías , Opacidad de la Córnea , Anomalías del Ojo , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Opacidad de la Córnea/terapia , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Anomalías del Ojo/terapia , Humanos , Lactante , Recién Nacido

RESUMEN

Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that shows greater severity in females and is largely attributed to mutations in EFNB1. A 7-year-old boy presented with hypertelorism, broad nasal root, midfacial hypoplasia, mandibular prognathia, ptosis, and scaphocephaly was clinically diagnosed with CFNS. Three-dimensional computed tomographic scans confirmed the isolated sagittal synostosis. His mother also showed clinical features of CFNS, but less severe. Genetic tests uncovered a novel C to T mutation at nucleotide 466 (c.466C>T) in exon 1 of EFNB1 for both. To the best of our knowledge, this is the only reported incident of CFNS in a male child exhibiting isolated sagittal synostosis.