RESUMO
Objective: The transcription factor OTX2 is implicated in ocular, craniofacial, and pituitary development. Design: We aimed to establish the contribution of OTX2 mutations in congenital hypopituitarism patients with/without eye abnormalities, study functional consequences, and establish OTX2 expression in the human brain, with a view to investigate the mechanism of action. Methods: We screened patients from the UK (n = 103), international centres (n = 24), and Brazil (n = 282); 145 were within the septo-optic dysplasia spectrum, and 264 had no eye phenotype. Transactivation ability of OTX2 variants was analysed in murine hypothalamic GT1-7 neurons. In situ hybridization was performed on human embryonic brain sections. Genetically engineered mice were generated with a series of C-terminal OTX2 variants. Results: Two chromosomal deletions and six haploinsufficient mutations were identified in individuals with eye abnormalities; an affected relative of one patient harboured the same mutation without an ocular phenotype. OTX2 truncations led to significant transactivation reduction. A missense variant was identified in another patient without eye abnormalities; however, studies revealed it was most likely not causative. In the mouse, truncations proximal to aa219 caused anophthalmia, while distal truncations and the missense variant were tolerated. During human embryogenesis, OTX2 was expressed in the posterior pituitary, retina, ear, thalamus, choroid plexus, and partially in the hypothalamus, but not in the anterior pituitary. Conclusions: OTX2 mutations are rarely associated with hypopituitarism in isolation without eye abnormalities, and may be variably penetrant, even within the same pedigree. Our data suggest that the endocrine phenotypes in patients with OTX2 mutations are of hypothalamic origin.
Assuntos
Hipopituitarismo/fisiopatologia , Microftalmia/fisiopatologia , Neurônios/fisiologia , Fatores de Transcrição Otx/genética , Hipófise/fisiopatologia , Displasia Septo-Óptica/fisiopatologia , Adolescente , Animais , Animais Geneticamente Modificados , Brasil , Linhagem Celular , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipopituitarismo/embriologia , Hipopituitarismo/genética , Hipotálamo/citologia , Lactente , Masculino , Camundongos , Microftalmia/embriologia , Microftalmia/genética , Mutação , Neurônios/patologia , Linhagem , Hipófise/embriologia , Hipófise/patologia , Displasia Septo-Óptica/embriologia , Displasia Septo-Óptica/genética , Reino UnidoRESUMO
Nanophthalmos-4 is a rare autosomal dominant disorder caused by two known variations in TMEM98. An Austrian Caucasian pedigree was identified suffering from nanophthalmos and late onset angle-closure glaucoma and premature loss of visual acuity. Whole exome sequencing identified segregation of a c.602G > C transversion in TMEM98 (p.Arg201Pro) as potentially causative. A protein homology model generated showed a TMEM98 structure comprising α4, α5/6, α7 and α8 antiparallel helix bundles and two predicted transmembrane domains in α1 and α7 that have been confirmed in vitro. Both p.Arg201Pro and the two missense variations representing proline insertions identified previously to cause nanophthalmos-4 (p.Ala193Pro and p.His196Pro) are located in the charge polarized helix α8 (p.183-p210). Stability of the C-terminal alpha helical structure of TMEM98 is therefore essential to prevent the development of human nanophthalmos-4. Precise molecular diagnosis could lead to the development of tailored therapies for patients with orphan ocular disease.
Assuntos
Glaucoma de Ângulo Fechado/genética , Hiperopia/genética , Proteínas de Membrana/genética , Microftalmia/genética , Mutação de Sentido Incorreto , Transtornos da Visão/genética , Acuidade Visual/fisiologia , Adulto , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Arginina , Feminino , Cirurgia Filtrante , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Fechado/cirurgia , Humanos , Hiperopia/fisiopatologia , Hiperopia/cirurgia , Implante de Lente Intraocular , Masculino , Microftalmia/fisiopatologia , Microftalmia/cirurgia , Microscopia Acústica , Pessoa de Meia-Idade , Linhagem , Facoemulsificação , Prolina , Conformação Proteica em alfa-Hélice/genética , Microscopia com Lâmpada de Fenda , Transtornos da Visão/fisiopatologia , Sequenciamento do ExomaRESUMO
Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by biallelic pathogenic variants in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), variably associated with long bone hypoplasia, horseshoe kidney, venous anomalies, vertebral anomalies, developmental delay, and intellectual disability. Here, we report the case of a woman who interrupted her pregnancy after ultrasound scans revealed a depression of the frontal bone, posterior fossa anomalies, cerebral ventricular enlargement, cleft spine involving the sacral and lower-lumbar vertebrae, and bilateral microphthalmia. Micrognathia, four fingers in both feet and a slight tibial bowing were added to the clinical picture after fetal autopsy. Exome sequencing identified two variants in the SMOC1 gene, each inherited from one of the parents: c.709G>T - p.(Glu237*) on exon 8 and c.1223G>A - p.(Cys408Tyr) on exon 11, both predicted to be pathogenic by different bioinformatics software. Brain histopathology showed an abnormal cortical neuronal migration, which could be related to the SMOC1 protein function, given its role in cellular signaling, proliferation and migration. Finally, we summarize phenotypic and genetic data of known MLA cases showing that our case has some unique features (Chiari II malformation; focal neuropathological alterations) that could be part of the variable phenotype of SMOC1-associated diseases.
Assuntos
Micrognatismo/genética , Microftalmia/genética , Neurônios/patologia , Osteonectina/genética , Adulto , Alelos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Movimento Celular/genética , Criança , Consanguinidade , Éxons/genética , Feminino , Feto , Homozigoto , Humanos , Lactente , Deformidades Congênitas dos Membros , Masculino , Micrognatismo/diagnóstico , Micrognatismo/diagnóstico por imagem , Micrognatismo/fisiopatologia , Microftalmia/diagnóstico por imagem , Microftalmia/fisiopatologia , Mutação , Linhagem , Análise de Sequência de DNARESUMO
PURPOSE: To determine the child's and parental perception of functional visual ability (FVA), vision-related and health-related quality of life (VR-QoL, HR-QoL) in children with microphthalmia/anophthalmia/coloboma (MAC). METHODS: Between June 25, 2014, and June 3, 2015, we carried out a cross-sectional observational study at Moorfields Eye Hospital, London, UK, enrolling 45 children 2-16 years of age with MAC attending our clinics, and their parents. To assess FVA, VR-QoL, and HR-QoL we asked participants to complete three validated tools, the Cardiff Visual Ability Questionnaire for Children (CVAQC), the Impact of Vision Impairment for Children (IVI-C) instrument, and the PedsQL V 4.0. The main outcome measures were the FVA, VR-QoL, and HR-QoL scores, reported by children and parents. RESULTS: In children with MAC, FVA is moderately reduced, with a median CVAQC score of -1.4 (IQR, -2.4 to 0.4; range, -3.0 [higher FVA] to +2.8 [lower FVA]). VR-QoL and HR-QoL are greatly reduced, with an IVI-C median score of 63 (IQR, 52-66; normal VR-QoL, 96), a median self-reported PedsQL score of 77 (IQR, 71-90; normal HR-QoL, 100) and parental score of 79 (IQR, 61-93), and a family impact score of 81 (67-93). Psychosocial well-being scores are lower than physical well-being scores. Parents and children have a different perception of the impact of the condition on the child's HR-QoL. CONCLUSIONS: MAC has a significant impact on a child's FVA and QoL, similar to that described by children with acute lymphoblastic leukaemia and chronic systemic conditions. Children and families may benefit from psychosocial support.
Assuntos
Anoftalmia , Coloboma , Microftalmia , Qualidade de Vida , Transtornos da Visão/psicologia , Adolescente , Anoftalmia/fisiopatologia , Anoftalmia/psicologia , Criança , Pré-Escolar , Coloboma/fisiopatologia , Coloboma/psicologia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Microftalmia/fisiopatologia , Microftalmia/psicologia , Perfil de Impacto da Doença , Acuidade VisualRESUMO
A 6-month-old Leine sheep was presented because of dermal tissue located on the left eye. During the first examination, the animal was clinically silent, apart from the deformed eye. A corneal and conjunctival dermoid and blindness of the left eye were diagnosed. Over a period of a year, the animal displayed conjunctivitis and inflammation of the affected eye. Furthermore, the sheep did not develop according to its age. During histopathological examination of the euthanized animal, microphthalmia and aphakia of the left eye were found in addition to the dermoids. Dermoids are described in humans and in different domestic animals. They can be combined with other congenital malformations. In sheep, dermoids are rarely diagnosed or reported in the literature.
Assuntos
Cisto Dermoide/veterinária , Neoplasias Oculares/veterinária , Doenças dos Ovinos/diagnóstico , Animais , Cisto Dermoide/diagnóstico , Cisto Dermoide/fisiopatologia , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/fisiopatologia , Microftalmia/diagnóstico , Microftalmia/fisiopatologia , Microftalmia/veterinária , Ovinos , Doenças dos Ovinos/fisiopatologiaRESUMO
Congenital growth hormone deficiency is a rare disorder with an incidence of approximately 1 in 4,000 live births. Pituitary development is under the control of a multitude of spatiotemporally regulated signaling molecules and transcription factors. Mutations in the genes encoding these molecules can result in hypopituitarism but for the majority of children with congenital hypopituitarism, the aetiology of their disease remains unknown. The proband is a 5-year-old girl who presented with neonatal hypoglycaemia and prolonged jaundice. No definitive endocrine cause of hypoglycaemia was identified in the neonatal period. She was born of normal size at 42 weeks but demonstrated growth failure with a progressive reduction in height to -3.2 SD by age 4.5 years and failed a growth hormone stimulation test with a peak growth hormone of 4.2 mcg/L. MRI of the pituitary gland demonstrated a hypoplastic anterior lobe and ectopic posterior lobe. Array CGH demonstrated an inherited 0.2 Mb gain at 1q21.1 and a de novo 4.8 Mb heterozygous deletion at 20p12.2-3. The deletion contained 17 protein coding genes including PROKR2 and BMP2, both of which are expressed during embryological development of the pituitary gland. PROKR2 mutations have been associated with hypopituitarism but a heterozygous deletion of this gene with hypopituitarism is a novel observation. In conclusion, congenital hypopituitarism can be present in individuals with a 20p12.3 deletion, observed with incomplete penetrance. Array CGH may be a useful investigation in select cases of early onset growth hormone deficiency, and patients with deletions within this region should be evaluated for pituitary hormone deficiencies.
Assuntos
Proteína Morfogenética Óssea 2/genética , Nanismo Hipofisário/genética , Hipopituitarismo/genética , Microftalmia/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 20/genética , Hibridização Genômica Comparativa , Nanismo Hipofisário/fisiopatologia , Desenvolvimento Embrionário/genética , Feminino , Heterozigoto , Humanos , Hipopituitarismo/fisiopatologia , Microftalmia/fisiopatologia , Mutação , Hipófise/anormalidades , Hipófise/crescimento & desenvolvimentoRESUMO
The aim of this study was to illustrate the surgical techniques and utility of stereotactic or image-guided navigation in the management of lacrimal drainage obstruction in congenital arhinia-microphtalmia syndrome and review the relevant literature. Image-guided combined external and endoscopic dacryocystorhinostomy was performed in a female, aged 16 years with congenital partial arhinia and ipsilateral microphthalmus. The lacrimal sac was bypassed to the contra lateral nasal cavity through a septal window. The surgical procedure was performed using the intra-operative optical image-guided Nav 1 PicoTM ENT navigation system with real-time intra-operative instrument geometry. Different phases of the surgical technique, adjunctive endoscopic procedures, intra-operative anatomical guidance, and utility at crucial phases of surgery were noted. A review of the literature was performed pertinent to arhinia and navigation guided lacrimal surgeries. Lacrimal bypass into the contra lateral nasal cavity even through a malformed septum is possible in partial arhinia syndromes. Detailed preoperative evaluation including 3D imaging studies, navigation guided planning of risk structures with intra-operative distance control and construction of meticulous surgical roadmaps were found to be essential factors in successful outcomes. At six months follow up after surgery, there was a complete and contiguous healed mucosal anastomosis with lacrimal system patent on irrigation and resolution of epiphora. Combined external and endoscopic approach is useful in partial arhinia syndromes. Image guidance is a very useful adjunctive tool that facilitates safe and precise surgery in the management of such complex lacrimal surgeries.
Assuntos
Dacriocistorinostomia/métodos , Anormalidades do Olho/cirurgia , Obstrução dos Ductos Lacrimais/terapia , Microftalmia/cirurgia , Ducto Nasolacrimal/anormalidades , Cirurgia Assistida por Computador , Adolescente , Endoscopia , Anormalidades do Olho/fisiopatologia , Feminino , Humanos , Obstrução dos Ductos Lacrimais/fisiopatologia , Microftalmia/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
We report the case of a 7-month-old girl with atypical oculo-facio-cardio-dental syndrome (OFCD). A novel de novo pathogenic mutation in the BCL6 interacting co-repressor gene (BCOR) (c.4540C>T; p.Arg1514*), was identified on the X chromosome. This case expands the phenotype of OFCD as it is the first report of a case presenting with craniosynostois, temporal hypertrichosis, supraorbital grooving, and underdevelopment of the midface.
Assuntos
Catarata/congênito , Craniossinostoses/genética , Defeitos dos Septos Cardíacos/genética , Microftalmia/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Catarata/genética , Catarata/fisiopatologia , Craniossinostoses/fisiopatologia , Surdez/genética , Surdez/fisiopatologia , Feminino , Genes Ligados ao Cromossomo X , Defeitos dos Septos Cardíacos/fisiopatologia , Humanos , Hipertricose/genética , Hipertricose/fisiopatologia , Lactente , Microftalmia/fisiopatologia , FenótipoRESUMO
PURPOSE: To provide guidelines for safe implantation of glaucoma drainage devices (GDDs) in small and pediatric eyes to avoid contact between the optic nerve (ON) and the posterior edge of the GDD plate. METHODS: We developed a formula for calculating limbus-to-ON distance to estimate the available "real estate" for GDD placement in small eyes. The formula was validated using eyes of pediatric decedents undergoing clinical autopsy, with axial lengths (AL) of 15-24 mm. For each autopsy eye, we measured AL, anterior chamber depth, corneal diameter, and limbus-to-ON distances for the four eye quadrants. The main outcome measure was the degree of agreement between measured and calculated limbus-to-ON distances. RESULTS: A total of 15 autopsy eyes were divided into derivation (n = 10) and validation (n = 5) groups. A formula was derived to estimate superotemporal limbus-to-ON distance (DST) using AL and corneal diameter data. Linear regression showed excellent correlation between the measured DST and AL (R2 = 0.98). There was excellent agreement between measured and calculated limbus-to-ON values for all four eye quadrants (R2 range, 0.92-0.98). CONCLUSIONS: Our formula accurately predicts limbus-to-ON distances across a wide range of clinically relevant ALs. Based on this information, GDD surgery in small eyes can be adjusted by positioning the GDD closer to the limbus or by trimming the posterior edge of the GDD plate. To our knowledge, this is the first set of guidelines developed to promote safe implantation of GDDs in small eyes.
Assuntos
Técnicas de Apoio para a Decisão , Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Limbo da Córnea/patologia , Microftalmia/cirurgia , Nervo Óptico/patologia , Implantação de Prótese/normas , Adolescente , Comprimento Axial do Olho/patologia , Criança , Pré-Escolar , Drenagem/instrumentação , Feminino , Glaucoma/fisiopatologia , Humanos , Lactente , Recém-Nascido , Pressão Intraocular/fisiologia , Masculino , Microftalmia/fisiopatologiaRESUMO
In the 30 years since the Chornobyl nuclear power plant disaster, there is evidence of persistent levels of incorporated ionizing radiation in adults, children and pregnant women in the surrounding area. Measured levels of Cesium-137 vary by region, and may be influenced by dietary and water sources as well as proximity to nuclear power plants. Since 2000, comprehensive, population-based birth defects monitoring has been performed in selected regions of Ukraine to evaluate trends and to generate hypotheses regarding potential causes of unexplained variations in defect rates. Significantly higher rates of microcephaly, neural tube defects, and microphthalmia have been identified in selected regions of Ukraine collectively known as Polissia compared to adjacent regions collectively termed non-Polissia, and these significantly higher rates were evident particularly in the years 2000-2009. The Polissia regions have also demonstrated higher mean whole body counts of Cesium-137 compared to values in individuals residing in other non-Polissia regions. The potential causal relationship between persistent ionizing radiation pollution and selected congenital anomaly rates supports the need for a more thorough, targeted investigation of the sources of persistent ionizing radiation and the biological plausibility of a potential teratogenic effect.
Assuntos
Contaminação Radioativa do Ar/efeitos adversos , Radioisótopos de Césio/efeitos adversos , Acidente Nuclear de Chernobyl , Teratogênese/efeitos da radiação , Radioisótopos de Césio/isolamento & purificação , Feminino , Humanos , Microcefalia/epidemiologia , Microcefalia/etiologia , Microcefalia/fisiopatologia , Microftalmia/epidemiologia , Microftalmia/etiologia , Microftalmia/fisiopatologia , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/fisiopatologia , Gravidez , UcrâniaRESUMO
PURPOSE: To study the characteristics of orbital cyst associated with microphthalmos in a group of Chinese patients, and to analyze the relationship between orbital cyst and orbital volume. DESIGN: Cross-sectional comparative study. PARTICIPANTS: 120 patients who were diagnosed as unilateral clinical blind microphthalmos, in which 20 patients had orbital cyst in the affected eye. METHOD: Participants had computed tomography (CT) scan. CT images were analyzed with a computer-aided software. MAIN OUTCOME MEASURES: Volume and position of orbital cyst, microphthalmic to contralateral ratio (MCR) of orbital volume, height and depth and orbital rim displacement. RESULTS: 38.1% of the cysts located anterior to or at the equator of the globe, 75% of which located infratemporally and all of which were outside the muscle cone. Most (84.6%) of the posterior cysts were inside the muscle cone. The anterior cysts were larger than the posterior cysts (p = 0.005). MCR of orbital volume (p<0.001), height (p = 0.004) and width (p = 0.043) were significantly higher in patients with orbital cyst than controls. For patients with orbital cyst, larger cyst-plus-globe volume of the affected eye was associated with higher MCR of orbital volume (r = 0.630, p = 0.003). Patients with large cyst-plus-globe volume had higher MCR of orbital volume (p = 0.002), height (p = 0.014), width (p = 0.005) and depth (p = 0.002) and less displacement in inferior (p = 0.004) orbital rim, compared with patients with small cyst-plus-globe volume, but the differences between patients with small cyst-plus-globe volume and patients without cyst were not significant. CONCLUSIONS: Microphthalmic eyes with large cyst-plus-globe volume showed better similarity with the contralateral eyes, comparing with microphthalmic eyes without orbital cyst or with small cyst-plus-globe volume. It suggested that the existence of orbital cysts (especially large cysts) in microphthalmic eyes might play a positive role in the orbital development.
Assuntos
Cegueira/fisiopatologia , Olho/fisiopatologia , Imageamento por Ressonância Magnética , Microftalmia/diagnóstico , Adolescente , Adulto , Cegueira/diagnóstico por imagem , Criança , Pré-Escolar , China , Cistos/diagnóstico por imagem , Cistos/fisiopatologia , Olho/diagnóstico por imagem , Feminino , Humanos , Lactente , Masculino , Microftalmia/fisiopatologia , Órbita/diagnóstico por imagem , Órbita/fisiopatologia , Doenças Orbitárias/diagnóstico por imagem , Doenças Orbitárias/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To evaluate the refractive and postoperative outcomes of a high-power foldable intraocular lens (IOL) in nanophthalmic eyes. SETTING: Six ophthalmic surgical centers in Canada. DESIGN: Retrospective case series. METHODS: Consecutive charts of nanophthalmic patients having cataract extraction and insertion of the CT Xtreme D IOL were reviewed. Demographic and clinical data were collected, including age, sex, axial length (AL), minimum keratometry (K) value and maximum K value, corneal white-to-white (WTW), anterior chamber depth, lens thickness (LT), and complications. The following preoperative and operative data were collected: uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA), sphere, cylinder, and spherical equivalence (SE). The primary outcome measure was change in SE. The secondary outcome measures were changes in UDVA and CDVA. RESULTS: A total of 21 eyes from 13 patients with a mean follow-up time of 9.6 ± 8.5 months were studied. Mean preoperative data were: age (51.4 ± 15.2 years), AL (16.63 ± 0.68 mm), minimum K value (46.20 ± 2.26 D), maximum K value (47.55 ± 2.34 D), anterior chamber depth (2.60 ± 0.49 mm), WTW (11.08 ± 1.38 mm), LT (4.70 ± 0.97 mm), and IOL power implanted (+49.9 ± 3.3 diopters [D]). SE improved from +16.11 ± 3.26 D preoperatively to +2.00 ± 2.37 D postoperatively (P < .0001). UDVA improved from 1.47 ± 0.30 logMAR preoperatively to 0.74 ± 0.43 logMAR postoperatively (P = .016). CDVA did not change significantly. Five eyes (23.8%) had serious postoperative complications. Of these eyes, 2 had malignant glaucoma, 2 had vitreous hemorrhages, and 1 eye had a vitreous hemorrhage with retinal detachment resulting in visual acuity of no light perception. CONCLUSION: Implanting foldable high-power IOLs in a series of nanophthalmic eyes yielded significant improvement in UDVA and SE. Cataract surgery in these eyes carries increased risk. FINANCIAL DISCLOSURE: Iqbal Ike K. Ahmed is a consultant to Carl Zeiss Meditec AG. No other author has a financial or proprietary interest in any material or method mentioned.
Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Microftalmia/cirurgia , Facoemulsificação , Refração Ocular/fisiologia , Acuidade Visual/fisiologia , Adulto , Idoso , Câmara Anterior/patologia , Comprimento Axial do Olho/patologia , Feminino , Seguimentos , Humanos , Masculino , Microftalmia/fisiopatologia , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To evaluate the long-term impact of bilateral cataract surgery on postoperative complications, influence of age at surgery on the pattern of axial growth and central corneal thickness (CCT), and visual and orthoptic assessment in microphthalmic eyes. SETTING: Iladevi Cataract and IOL Research Centre, Ahmedabad, India. DESIGN: Prospective longitudinal study. METHODS: This study assessed children with microphthalmos who had bilateral congenital cataract surgery. Microphthalmos was defined as an eye that has an axial length (AL) that was 2 standard deviations smaller than what is normally expected at that age. All eyes were left aphakic. One of the 2 eyes was randomly selected for analysis. Postoperative complications, AL, CCT, and visual acuity were documented. RESULTS: This study included 72 eys of 36 children. The mean age of the patients was 4.8 months ± 6.2 (SD) (range 0.5 to 15 months). Postoperative complications included secondary glaucoma (11/36, 30.6%), visual axis obscuration (4/36, 11.1%), and posterior synechiae (10/36, 27.8%). A significant rate of change was observed in axial growth up to 4 years and in CCT up to 3 years postoperatively. When age at the time of surgery was correlated with the profile of the rate of change in AL and CCT at 1 month and 1, 2, and 4 years, statistically significant differences in AL and CCT at all timepoints were found. Loss of vision after surgery occurred in 2 eyes. CONCLUSION: After early surgical intervention, an acceptable rate of serious postoperative complications and good visual outcomes were obtained in microphthalmic eyes. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
Assuntos
Extração de Catarata/métodos , Catarata/congênito , Microftalmia/cirurgia , Complicações Pós-Operatórias , Afacia Pós-Catarata/etiologia , Afacia Pós-Catarata/fisiopatologia , Comprimento Axial do Olho/patologia , Catarata/fisiopatologia , Córnea/patologia , Paquimetria Corneana , Feminino , Seguimentos , Humanos , Lactente , Pressão Intraocular/fisiologia , Masculino , Microftalmia/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To report new aspects of the phenotype including Retinal dystrophy and surgical challenges in Hallermann-Streiff Francois syndrome (HSFS). METHODS: Detailed phenotype of a female with HSFS was evaluated including skeletal changes, comprehensive eye examination, detailed ocular biometry, electroretinography and macular Ocular coherence tomography. Surgical notes of lid surgery for entropion were reviewed. Genetic screening was also done. RESULTS: Unique Ocular biometry with electroretinography changes, macular folds and fundus changes suggestive of an unreported Retinal dystrophy in a typical patient with HSFS were noted. Surgery was challenging both due to difficulty in endotracheal intubation anaesthesia because of the dento-facial abnormalities and the skin fragility. CONCLUSION: This report provides additional information especially pigmentary retinal dystrophy, macular folds and electroretinography in HSFS. The microphthalmos had overlapping posterior segment findings usually reported with Nanophthalmos and Posterior microphthalmos. The surgical difficulties and outcomes of the rarely encountered adnexal abnormalities emphasize the need for a multi disciplinary approach for appropriate management.
Assuntos
Eletrorretinografia , Entrópio/etiologia , Síndrome de Hallermann/complicações , Microftalmia/etiologia , Distrofias Retinianas/etiologia , Biometria , Conexina 43/genética , Entrópio/cirurgia , Feminino , Síndrome de Hallermann/genética , Síndrome de Hallermann/fisiopatologia , Humanos , Microftalmia/genética , Microftalmia/fisiopatologia , Procedimentos Cirúrgicos Oftalmológicos , Fenótipo , Estimulação Luminosa , Retina/fisiopatologia , Distrofias Retinianas/genética , Distrofias Retinianas/fisiopatologia , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Oculo-facio-cardio-dental (OFCD) syndrome is a rare syndrome characterized by ocular, facial, cardiac, and dental disorders. Only about 20 cases have been reported to date. The most prominent of the various features of this syndrome is canine radiculomegaly. Other features include a long and narrow face, a high nasal bridge, a broad and pointed nose, a bifid nose, ear deformity, cleft palate or submucous cleft palate, maxillary growth retardation, a large gonial angle, open apices, delayed eruption, persistent deciduous teeth, extreme overbite, and constricted maxilla. Orthodontic and prosthodontic treatment has been reported for several patients, but surgical-orthodontic treatment for OFCD has not been reported. An 18-year-old woman with skeletal Class III malocclusion and OFCD syndrome was treated with edgewise appliance therapy combined with orthognathic surgery. We applied a light force during the treatment so as not to induce ankylosis. At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. After the retention period, stomatognathic function was improved. The results of this treatment suggest that surgical-orthodontic treatment is an effective method for improving skeletal disharmony, facial profile, occlusion, and stomatognathic function in patients with OFCD.
Assuntos
Cardiopatias Congênitas/cirurgia , Má Oclusão Classe III de Angle/terapia , Microftalmia/cirurgia , Ortodontia Corretiva , Osteotomia Sagital do Ramo Mandibular , Anormalidades Dentárias , Raiz Dentária/anormalidades , Adolescente , Dente Pré-Molar/anormalidades , Encéfalo/anormalidades , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Catarata/fisiopatologia , Catarata/terapia , Cefalometria , Dente Canino/anormalidades , Feminino , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Defeitos dos Septos Cardíacos , Humanos , Má Oclusão/terapia , Má Oclusão Classe III de Angle/cirurgia , Mastigação , Microftalmia/fisiopatologia , Microftalmia/terapia , Odontometria , Técnica de Expansão Palatina , Adulto JovemRESUMO
PURPOSE: To compare the refractive outcome and postoperative complications of cataract surgery among nanophthalmos and relative anterior microphthalmos and the normal control eyes. DESIGN: Retrospective case-control series. METHODS: Seventeen eyes with nanophthalmos, 29 eyes with relative anterior microphthalmos, and 54 normal control eyes were enrolled in this study. The subjects were divided into 3 diagnostic subgroups according to the following: nanophthalmos with an axial length <20.5 mm and without morphologic malformation; relative anterior microphthalmos with a corneal diameter (CD) ≤ 11 mm, an anterior chamber depth (ACD) ≤ 2.2 mm, and an axial length (AL) ≥ 20.5 mm; and normal control group eyes defined as an AL ≥ 20.5 mm with a CD >11 mm or an ACD >2.2 mm. The implanted intraocular lens (IOL) power was used to calculate the predicted postoperative refraction error according to 4 IOL power formulas: SRK II, SRK/T, Hoffer Q, and Holladay 1. With each formula, the mean numeric error and mean absolute error were calculated. At postoperative 2 months, the endothelial cell count and the complications were analyzed. RESULTS: As measured by mean numeric error or mean absolute error, there was a significant difference among the 3 groups based on SRK II, SRK/T, and Hoffer Q, with less predictability in the nanophthalmic eyes. In eyes with nanophthalmos, the Holladay 1 produced the best refractive results as measured by mean numeric error (P < .001). A higher occurrence rate of posterior capsule rupture (11.7%) was shown in the nanophthalmic eyes. The difference among the 3 groups for the postoperative endothelial cell loss was not significant (P = .421). CONCLUSIONS: The refractive predictability and postoperative outcome was poorer in the eyes with nanophthalmos compared to the eyes with relative anterior microphthalmos or normal control.
Assuntos
Segmento Anterior do Olho/anormalidades , Implante de Lente Intraocular , Microftalmia/cirurgia , Facoemulsificação/métodos , Idoso , Comprimento Axial do Olho/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Microftalmia/fisiopatologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Refração Ocular/fisiologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. METHODS: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. RESULTS: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III:1; III:2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2) and in unaffected I:1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. CONCLUSIONS: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Proteínas do Olho/genética , Microftalmia/genética , Nervo Óptico , Doenças Assintomáticas , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 10/química , Cromossomos Humanos Par 10/genética , Família 26 do Citocromo P450 , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Genes Dominantes , Ligação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Microftalmia/fisiopatologia , Pessoa de Meia-Idade , Mutação , Neuroimagem , Nervo Óptico/anormalidades , Nervo Óptico/metabolismo , Linhagem , Fenótipo , Ácido Retinoico 4 Hidroxilase , Tretinoína/metabolismo , Testes VisuaisRESUMO
BACKGROUND: Lenz microphthalmia syndrome is an X-linked recessive disorder characterized by microphthalmia and dental, urogenital, and skeletal anomalies. This case report represents the first detailed account of congenital kyphoscoliosis in the Lenz microphthalmia literature. METHODS: We present a case of Lenz microphthalmia syndrome with progressive kyphosis, spinal stenosis, and late-onset tibia vara along with many of the typical features of the disorder. In addition, we provide insight into the syndrome by reviewing the existing Lenz microphthalmia literature. RESULTS: Congenital kyphoscoliosis that is prone to reoccurrence after posterior spinal fusion is an unusual entity that may be associated with Lenz microphthalmia. CONCLUSIONS: We recommend close monitoring and early surgical intervention with posterior spinal fusion for congenital kyphosis in patients diagnosed with Lenz microphthalmia syndrome. However, more data on similar patients are necessary to define the optimal treatment strategy. LEVEL OF EVIDENCE (FOR CLINICAL ARTICLES): Level V.
Assuntos
Anoftalmia/fisiopatologia , Cifose/congênito , Microftalmia/fisiopatologia , Escoliose/congênito , Adolescente , Anoftalmia/cirurgia , Doenças do Desenvolvimento Ósseo/congênito , Doenças do Desenvolvimento Ósseo/cirurgia , Seguimentos , Humanos , Cifose/cirurgia , Masculino , Microftalmia/cirurgia , Osteocondrose/congênito , Osteocondrose/cirurgia , Escoliose/cirurgia , Fusão Vertebral/métodos , Estenose Espinal/congênito , Estenose Espinal/cirurgiaRESUMO
AIM: To report clinical findings relating to the lacrimal system in congenital clinical anophthalmos and severe blind microphthalmos. METHODS: A retrospective (up to 2003) and prospective (2004 onwards) study of the notes of 60 consecutive patients treated surgically with highly hydrophilic self-inflating expanders for congenital anophthalmos or severe blind microphthalmos between 1997 and 2006. The lacrimal drainage system was always probed and irrigated under general anaesthesia before any other procedure was started. RESULTS: Nine patients were excluded due to possible misdiagnosis because of previous lid or orbit surgery elsewhere or due to missing data. The analysis therefore included 23 girls and 28 boys aged between 1 and 90 months (median age: 4 months). Twenty-three patients presented with unilateral and 18 with bilateral anophthalmos, and 10 had unilateral microphthalmos; consequently, 102 orbits (of which, 69 were with probable pathology) were available for assessment. In unilateral cases, the lacrimal system on the normal side was never affected. On the anophthalmic or microphthalmic side, the lacrimal system was normal in 17 orbits only (24.6%). The most frequent finding was canalicular stenosis (40 orbits; 58%). Common canaliculus stenosis was observed in 5 orbits (7.3%) and nasolacrimal duct obstruction in 7 orbits (10.1%). There were no cases of punctal anomaly. CONCLUSIONS: In congenital clinical anophthalmos the lacrimal system is affected in up to 78% of cases, mostly due to canalicular stenosis. Even if there is no clear evidence of an embryological connection, this association is certainly not a random finding.
Assuntos
Anoftalmia/fisiopatologia , Cegueira/etiologia , Cegueira/fisiopatologia , Aparelho Lacrimal/fisiopatologia , Microftalmia/complicações , Microftalmia/fisiopatologia , Anoftalmia/complicações , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Obstrução dos Ductos Lacrimais/etiologia , Masculino , Ducto Nasolacrimal , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: The purpose of this study is to identify the characteristics of strabismus that coexist with nanophthalmos and to report the results of strabismus surgery performed on these small eyes. DESIGN: Retrospective, consecutive, noncomparative interventional case series. PARTICIPANTS: Fifteen bilateral nanophthalmic patients, of whom five underwent horizontal muscle surgery, were included in this study. METHODS: Chart review. The clinical examination included visual acuity assessments using the linear Snellen and the Lea charts, slit-lamp and fundus examinations, intraocular pressure, and axial length measurements. The orthoptic examination consisted of measurements of ocular deviations using the prism cover test with an accommodative target at both near and distance with and without refractive correction, assessment of ocular motility with ductions and versions, binocularity with Worth's four-dot test, and the Titmus test. Amblyopia was treated with part-time occlusion. Surgery for the correction of esotropia included bilateral medial rectus recessions or recess-resect procedures. MAIN OUTCOME MEASURES: Magnitude of strabismic deviation, best-corrected visual acuity, and the level of binocular vision achieved were monitored. RESULTS: The average age of enrollment in the study was 4.7 (range, 1-12) years. The patients were followed for an average of 7.0 (range, 4-14) years. The mean axial length was determined as 18.4 mm (range, 15.5-20.7). The mean refractive error in spherical equivalents was measured as +9.9 and ranged between +4.0 and +15.0 diopters. Five patients (33%) had nonaccommodative esotropia, four (27%) had partially refractive esotropia, four (27%) had microesotropia, and two (13%) had exotropia. Five patients, all having nonaccommodative esotropia, underwent surgery for the correction of ocular misalignment. Diminishing the surgical dose in these small eyes resulted in undercorrections. Despite patching, 3 patients (20%) had unilateral and 12 patients (80%) had bilateral amblyopia at the conclusion of the study. CONCLUSIONS: Strabismus in nanophthalmos usually manifests as nonaccommodative and partially refractive esotropia. Medial rectus recession should be applied with care to prevent adduction deficit and convergence insufficiency. Otherwise, there seems to be no need for decreasing the surgical dose with regard to the smaller axial length. Amblyopia tends to be persistent in these patients.