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PURPOSE: Blue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI. To address this medical need, this study is aimed to design and validate a new method called 'BLUES' (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI. METHODS: Sixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed. In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the 'BLUES' procedure to the judgement of experienced ophthalmologists (JEO). A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of 'BLUES' and 'JEO' were estimated versus the standard OI diagnosis. The K indexes of 'BLUES' versus 'JEO' were also evaluated. RESULTS: The optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835-0.945) and specificity of 87% (CI95%: 0.791-0.949) for the 'BLUES' procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of 'JEO' ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between 'BLUES 'and 'JEO' evaluations ranged from 0.613 to 0.734. CONCLUSIONS: Our findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The 'BLUES' procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI.
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Osteogénesis Imperfecta , Esclerótica , Humanos , Osteogénesis Imperfecta/patología , Osteogénesis Imperfecta/diagnóstico , Esclerótica/patología , Femenino , Masculino , Estudios Prospectivos , Adolescente , Niño , Adulto , Adulto Joven , Preescolar , Curva ROCRESUMEN
BACKGROUND: Variations in ZNF469 have been associated with Brittle Cornea Syndrome that presents with bluish sclera, loss of vision after trivial trauma, arachnodactyly, and joint laxity. MATERIALS AND METHODS: Detailed medical and family history, physical examination, and molecular analysis. RESULTS: A 21-year-old female presented with bluish discoloration of sclera, diminution of vision following trivial trauma in childhood along with hearing loss and systemic features of arachnodactyly and joint laxity. Clinical diagnosis of brittle cornea syndrome was made which was molecularly proven using next-generation sequencing which identified compound heterozygosity in ZNF469 for pathogenic and likely pathogenic nonsense variants. One variant namely NM_001367624.2:c.5882dup was identified in the exon 3 which was novel and classified as likely pathogenic according to American College of Medical Genetics (ACMG) criteria for variant classification. Another variant NM_001367624.2:c.8992C>T in the exon 2 was classified as pathogenic for Brittle Cornea Syndrome 1. CONCLUSIONS: The report adds to the allelic heterogeneity in ZNF469 causative of Brittle Cornea Syndrome 1 and shall acquaint the physicians about this potentially vision threatening, underdiagnosed, rare syndrome.
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Alelos , Inestabilidad de la Articulación , Factores de Transcripción , Humanos , Femenino , Adulto Joven , Factores de Transcripción/genética , Inestabilidad de la Articulación/genética , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/congénito , India , Anomalías Cutáneas/genética , Anomalías Cutáneas/diagnóstico , Aracnodactilia/genética , Aracnodactilia/diagnóstico , Enfermedades del Tejido Conjuntivo/genética , Enfermedades del Tejido Conjuntivo/diagnóstico , Anomalías del Ojo/genética , Anomalías del Ojo/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Linaje , Mutación , Exones/genética , Anomalías Múltiples/genética , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/diagnóstico , Enfermedades Cutáneas Genéticas/genética , Enfermedades Cutáneas Genéticas/diagnóstico , Enfermedades Cutáneas Genéticas/patologíaRESUMEN
It concerns three siblings (two 28 year old twin boys and a 25 year old woman) who presented a previous history of rupture of eyeball in one eye and very poor vision in the other. At the first ophthalmoscopic and instrumental evaluation, three patients presented with bluish sclera and keratoglobus in the intact eye. A genetic analysis with whole exome sequencing was then performed on the three siblings, identifying a biallelic variant of the PRDM5 gene that led to the diagnosis of Brittle Cornea Syndrome (BCS), a rare autosomal recessive disorder characterized by corneal thinning and blue sclera. To preserve the only intact eye from possible breakage, the three siblings were trained in using protective measures (polycarbonate goggles etc.) to carry out close monitoring of symptoms and were asked to continue with follow-up visits for ocular and systemic diseases associated with BCS. Given the poor best corrected visual acuity achievable with glasses and contact lenses, penetrating keratoplasty was performed, achieving good visual acuity maintained in the 2-year follow-up in two of the three patients. Knowledge of this pathology and its clinical manifestations is essential for early diagnosis and correct management of this rare but very debilitating pathology. To our knowledge, this is the first case series of BCS reported in an Albanian population.
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Anomalías del Ojo , Inestabilidad de la Articulación , Anomalías Cutáneas , Masculino , Femenino , Humanos , Adulto , Queratoplastia Penetrante , Anomalías Cutáneas/diagnóstico , Anomalías Cutáneas/genética , Anomalías Cutáneas/cirugía , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Anomalías del Ojo/cirugía , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/genética , Inestabilidad de la Articulación/cirugía , Córnea/patologíaRESUMEN
BACKGROUND: A report of a Brittle cornea syndrome (BCS) case with bluish scleral discoloration, keratoglobus, and myopia based on multimodal imaging modalities including in vivo confocal microscopy (IVCM), high-definition optical coherence tomography (HD-OCT) and scheimpflug corneal densitometry analysis. CASE PRESENTATION: A 36-year-old Chinese female patient presented with significant bluish discoloration of the sclera in both eyes, extreme corneal thinning with increased corneal curvature, increased central corneal densitometry, and nystagmus. She also had scoliosis, severe osteoporosis, and thyroid disease. CONCLUSIONS: Timely diagnosis, early detection, and detailed follow-up are essential for BCS. There has been no report of a BCS evaluation performed by IVCM and corneal densitometry methods thus far in the literature. Furthermore, multimodal imaging can offer a more comprehensive view of BCS and contribute to a deeper understanding of the disease. Interestingly, this is a rare case of BCS in an adult with good vision, an intact cornea, and nystagmus.
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Miopía , Nistagmo Patológico , Adulto , Femenino , Humanos , Córnea/diagnóstico por imagen , Pueblo Asiatico , Imagen MultimodalRESUMEN
BACKGROUND: Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility. Type I OI is the most common type of OI, and is autosomal dominantly-inherited. Type I OI develops due to pathogenic variants in the collagen 1 Alpha 1 (COL1A1) gene on chromosome 17. Collagen proteins are important components of the extracellular matrix of the trabecular meshwork, Schlemm's canal, and lamina cribrosa, which play a role in the development of glaucoma. PURPOSE: To report a father and his daughter who were diagnosed with glaucoma and OI type I. MATERIALS AND METHODS: Case report. RESULTS: A 58-year-old man and his 31-year-old daughter were diagnosed with OI type 1 [NM_000088.4 (COL1A1): c.3008del (p.Pro1003fs)]. In addition, both subjects had glaucomatous optic neuropathy. CONCLUSIONS: In this report, we presented a pathogenic variant in a father and his daughter with OI and coexisting glaucoma. The abnormalities in collagen may contribute to the risk of glaucoma development in patients with COL1A1-associated OI. Therefore, screening for glaucoma may be indicated when caring for patients with this diagnosis.
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Glaucoma , Osteogénesis Imperfecta , Masculino , Humanos , Persona de Mediana Edad , Adulto , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo I/genética , Colágeno/genética , Glaucoma/genética , MutaciónRESUMEN
Brittle cornea syndrome (BCS) is a genetic connective tissue disorder with discernible ocular features such as blue scleral and thin cornea that predominantly presents in younger children. We herein describe cases of three siblings with BCS, two of whom presented to us with open globe injuries following trivial trauma. Clinical examination of the other eye in both showed diffusely thin corneas and blue sclera. A systemic evaluation revealed sensorineural hearing loss and hyperextensible joints. The third sibling was screened and found to have features concurrent with BCS. This report highlights the challenges faced in the management of ocular injuries and consecutive complications in these patients.
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Anomalías del Ojo , Inestabilidad de la Articulación , Anomalías Cutáneas , Niño , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Humanos , Inestabilidad de la Articulación/congénito , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/genética , Masculino , Hermanos , Anomalías Cutáneas/diagnóstico , Anomalías Cutáneas/genéticaRESUMEN
Purpose: Hallermann-Streiff syndrome (HSS) is a rare congenital disorder characterized by dyscephaly, hypotrichosis, microphthalmia, dental anomalies, and cutaneous atrophy. Because of the presence of a characteristic facial appearance, severe visual disturbance, and/or upper airway obstruction, most patients with HSS are diagnosed as having a congenital anomaly as a newborn or early in life. We report a case of HSS that was first recognized when the patient was in her seventh decade of life. Observations: A 68-year-old woman presented to our department for decreased vision in both eyes (OU). Her ocular medical history included "ocular injections" in her left eye (OS); laser iridotomies OU, cataract surgery OS, and removal of corneal opacity OU; she did not have a remarkable systemic medical history. At the initial visit to our department, her best-corrected visual acuity was 0.5 in her right eye (OD) and 0.1 OS with +4.0-diopter hyperopic correction OU, corneal opacity due to calcification OU, a shallow anterior chamber and iridotrabecular contact OD were observed. During the surgical intervention OD, the surgeon recognized a "blue sclera," and the physicians initially suspected an underlying systemic malformation. Although mild, she presented with a thin beak-like nose and receding chin. In combination with the ocular features, the proportionate short stature, and a characteristic facial appearance, she was diagnosed with HSS. Conclusions and importance: Patients with HSS who had no clinically significant cosmetic, visual, and respiratory problems early in life may not be recognized as having HSS. The presence of corneal opacity, short axial length, and a blue sclera recognized by ophthalmologists can lead to the correct diagnosis of this congenital disorder.
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Brittle cornea syndrome is among the few special scenarios in ophthalmology that are a nightmare not only for the operating surgeon but also for the patient. Here, the thin and fragile corneas are unable to maintain the shape and structural integrity of the globe and are more prone to minor traumatic or spontaneous corneal perforations. Suturing a brittle cornea and closure of the corneal perforation in a brittle cornea are very challenging requiring the utmost care and special precautions. If proper measures are not taken during the surgery, it may be difficult to salvage the eye. Hence, it is imperative to diagnose appropriately, suture effectively, taking necessary preventive measures in salvaging these corneas. This manuscript aims at providing tips for handling brittle corneal perforations. It will also discuss the problems encountered during surgery, highlight the suturing techniques that can be customized, and finally give an insight into postoperative care.
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Perforación Corneal , Anomalías del Ojo , Anomalías Cutáneas , Córnea/cirugía , Perforación Corneal/diagnóstico , Perforación Corneal/etiología , Perforación Corneal/cirugía , Humanos , Técnicas de SuturaRESUMEN
Pellucid marginal corneal degeneration (PMCD) is a progressive corneal ectasia that ultimately results in high regular astigmatism and correction of this astigmatism is always challenging. However, when a PMCD patient develops a cataract, it provides a golden opportunity to treat this coexisting astigmatism with toric intraocular lens (IOL) implantation. Regular toric IOLs would correct astigmatism only up to 6 diopters in the IOL plane but higher astigmatism would require customization of such IOLs. Our case report describes the long term outcomes of customized toric IOL to tackle this high astigmatism during cataract surgery in PMCD cases.
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Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificación , Astigmatismo/complicaciones , Astigmatismo/cirugía , Catarata/complicaciones , Catarata/diagnóstico , Humanos , Implantación de Lentes Intraoculares , Refracción Ocular , Resultado del Tratamiento , Agudeza VisualRESUMEN
A 3-year-old girl presenting with blue sclera, hyperlaxity and developmental dysplasia of hip was found to have bilateral corneal thinning with astigmatism and keratoconus. By clinical exome sequencing, a frameshift mutation c.713_716 del TTTG p.(Val238Alafs*35) in PRDM5 gene causing brittle cornea syndrome 2 and a novel frameshift mutation c.401dup p.(Ser135Glufs*53) in SLC6A5 gene causing Hyperekplexia 3 were identified. No features of hyperekplexia were identified in proband. The novel homozygous mutation of SLC6A5 gene in the proband was presently asymptomatic but they were apprised of the possibility of developing neurological symptoms in the later years.
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Anomalías del Ojo , Queratocono , Preescolar , Córnea , Proteínas de Unión al ADN/genética , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Femenino , Proteínas de Transporte de Glicina en la Membrana Plasmática , Humanos , Inestabilidad de la Articulación/congénito , Mutación , Anomalías Cutáneas , Factores de Transcripción/genéticaRESUMEN
We report a case of bilateral displaced acetabular fractures including both columns fractures with protrusio acetabuli in a female patient, aged 15â¯years, with osteogenesis imperfecta (OI) (Sillence Type I), epilepsy, blue sclera and bilateral ipoacusia. Since OI is a rare genetic disorder characterized by an increased propensity to osteopenia, intraoperative fracture risks and hemorrhagic diathesis, we opted for the open reduction and internal fixation of the acetabula in two surgical steps and using two different approaches. Although the clinical outcomes are not excellent in this report (HHS 45/100), the authors suggest that chances of a good outcome with reconstruction of the acetabulum must be balanced against the benefits of early or late total hip arthroplasty. The goal was to delay a joint replacement as long as possible due to the patient's young age. Level of evidence: V, case report.
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PURPOSE: To evaluate the role of multimodal imaging in the diagnosis and monitoring of patients with osteogenesis imperfecta complicated with choroidal neovascularization. CASE REPORT: A 28-year-old man, diagnosed with osteogenesis imperfecta, was referred 2 months after the appearance of central scotoma and metamorphopsia in the right eye. The patient underwent a complete ophthalmological evaluation including visual acuity examination as well as ophthalmoscopy, spectral-domain optical coherence tomography, optical coherence tomography angiography, fundus autofluorescence imaging, fluorescein angiography and microperimetry. Complete examination revealed macular lacquer crack with subretinal haemorrhage. A further investigation with spectral-domain optical coherence tomography and fluorescein angiography revealed the presence of choroidal neovascularization without clear activity associated to the lacquer crack. After a 1-month follow-up, both visual acuity and retinal sensitivity improved spontaneously. CONCLUSION: Collagen deficiency of osteogenesis imperfecta leads to fragility of the Bruch's membrane; tension forces probably act at this level determining ruptures with bleeding and choroidal neovascularization formation. Multimodal imaging and functional evaluation are needed to assess retinal alterations in patients with osteogenesis imperfecta, whereas treatment of choroidal neovascularization should be reserved only for active lesion to prevent evolution and visual acuity decrement.
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Neovascularización Coroidal/diagnóstico por imagen , Imagen Multimodal , Osteogénesis Imperfecta/diagnóstico por imagen , Adulto , Neovascularización Coroidal/etiología , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Oftalmoscopía/métodos , Imagen Óptica , Osteogénesis Imperfecta/complicaciones , Tomografía de Coherencia Óptica/métodos , Agudeza Visual/fisiologíaRESUMEN
INTRODUCTION: The goal of this study was to describe and analyze the ophthalmological manifestations found in 21 patients followed for Ehlers-Danlos Syndrome in our department. METHODS: This retrospective study analyzed 21 consecutive patients (17 women and 4 men) with Ehlers-Danlos syndrome seen in the Necker hospital, Paris, between April 2016 and November 2017. The mean age was 25.95 years (12-47). A complete evaluation was performed searching for symptoms, orthoptic evaluation and complete ophthalmologic examination with slit lamp examination of the anterior segment, pachymetry and fundus examination with fundus photography and OCT. RESULTS: Nineteen patients presented ophthalmological signs (90.5%). The most frequent ophthalmological signs were: ocular motility disorders in 15 patients (71.4%), with convergence insufficiency in 13 of them, blue sclera in 8 patients (38%) and dry eye syndrome in 7 patients (33%, with 2 patients with reduced Break-Up Time<10seconds and 5 with very reduced Break-Up Time<5seconds). Mean pachymetry was 539.25µm (365-612). One patient presented with bilateral keratoglobus (4.8%). High myopia was present in 2 patients (9.5%) and associated with retinal tears in one patient (4.8%). No patients presented with angioid streaks. DISCUSSION: In this study, the main ophthalmological sign was convergence insufficiency present in more than 60% of the patients. This highlights the importance of an orthoptic examination in patients with Ehlers-Danlos syndrome. Dry eye syndrome with tear film instability was frequent, even though the patients were young. Blue sclera was seen in 38% of the patients. We reported two patients with high myopia and one patient with keratoglobus in our cohort. No patients presented with angioid streaks, and mean pachymetry was normal in our series. CONCLUSION: An ophthalmological and orthoptic evaluation should be performed in all patients with Ehlers-Danlos syndrome to detect and treat ocular manifestations. If Ehlers-Danlos syndrome is suspected, ophthalmological examination can also provide support for the diagnosis.
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Síndrome de Ehlers-Danlos/epidemiología , Oftalmopatías/epidemiología , Adolescente , Adulto , Niño , Estudios de Cohortes , Síndrome de Ehlers-Danlos/complicaciones , Oftalmopatías/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paris/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
We report the case of a 3-year-old boy presenting with bilateral keratoglobus and blue sclera in addition to hallux valgus, arachnodactyly, small joint hypermobility, mitral valve dysfunction and a history of generalized muscular hypotonia in early infancy. Molecular genetics provided evidence of two pathogenic mutations in the ZNF469 gene (compound heterozygosity) leading to the diagnosis of brittle cornea syndrome type 1. In addition to neuropediatric care, spectacles were prescribed to correct refractive error and for ocular protection. Owing to the thin cornea and sclera, eye injuries are the main cause for irreversible visual loss in this disease.
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Anomalías del Ojo , Inestabilidad de la Articulación/congénito , Anomalías Cutáneas , Factores de Transcripción/genética , Preescolar , Córnea , Anomalías del Ojo/genética , Humanos , Inestabilidad de la Articulación/genética , Masculino , Mutación , Anomalías Cutáneas/genéticaRESUMEN
BACKGROUND: To report a patient who presented with bluish scleral discoloration, keratoconus, and progressive high myopia. CASE PRESENTATION: A 6-year-old Chinese female patient presented with a significant bluish discoloration of the sclera in both eyes and extreme corneal thinning with anterior corneal protrusion. General pediatric physical examination was normal for all systems and no genetic disorders known were observed. CONCLUSIONS: We aim to highlight the importance of diagnosis and treatment of patients suffering from Brittle cornea syndrome. Timely diagnosis and early provision of protective glasses seem to be the most important step in treating BCS. To our knowledge, this is the first case of BCS being reported in the Asia area.
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Anomalías del Ojo/patología , Inestabilidad de la Articulación/congénito , Anomalías Cutáneas/patología , Niño , Diagnóstico Diferencial , Anomalías del Ojo/terapia , Dispositivos de Protección de los Ojos , Anteojos , Femenino , Humanos , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/terapia , Queratocono/patología , Miopía Degenerativa/patología , Esclerótica/patología , Anomalías Cutáneas/terapiaRESUMEN
Osteogenesis imperfecta (OI) is a rare genetically inherited syndrome involving connective tissues, resulting in anatomic and physiologic abnormalities, which results in any form of anesthesia, a challenging task. We hereby report a case of OI type I presented with distinctively blue sclera, hearing loss, kyphoscoliosis, and mild pulmonary restrictive disease who underwent rush nail removal in the femur.
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Keratoglobus is a rare condition of bilateral corneal ectasia, which results in high myopia, irregular astigmatism, scarring, and rarely spontaneous globe rupture. Globoid protrusion of a clear, diffusely thin cornea is the pathology. The congenital form has been associated with blue sclera in which there is a systemic connective tissue disorder with abnormal collagen synthesis like Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. Some concomitant abnormalities reported with kertoglobus include joint hypermobility, dental and skeletal abnormalities, osteal fragility, and deafness. Acquired forms have been reported to be associated with vernal keratoconjunctivitis and thyroid ophthalmopathy. We report the case of a 16-year-old boy with keratoglobus who presented with a history of photophobia and a low vision in both eyes since birth. He has been followed up by our pediatric cardiology department due to multiple cardiac anomalies. He had hypermobility of large joints, easy bruising, thin and hyperextensible skin with visible veins, which were also described in his elder brother. We aimed to discuss the etiology and the association of keratoglobus with some systemic abnormalities caused by collogen tissue disturbance, and make a brief review about the recent literature concerning the management of keratoglobus patients.