RESUMEN
Corneal dystrophies (CDs) represent a heterogenous group of genetic diseases (Lisch and Weiss, 2019). The International Committee of Classification of Corneal Dystrophies (IC3D) distinguishes between 22 distinct forms of corneal dystrophy (CD) which are predominantly autosomal dominant, although autosomal recessive and X-chromosomal dominant and recessive patterns do exist. A detailed corneal examination of as many affected family members as possible can show the phenotypic differences of the various generations. There are few publications which describe the different CDs with regard to the early and late phenotypes. According to early and late phenotype, three types of CD are generally classified: (1) Thirteen CDs with early and late clinical landmarks. However, it must be pointed out that the different penetrances of the gene often leads to quantitative differences in the corneal phenotype in peers in distinct generations of the same family. (2) Seven CDs with late onset and very little progression of the corneal changes. (3) Two CDs with congenital haze which can be interpreted as the final phenotype of this dystrophy. This applies to autosomal dominant and recessive inheritance.
Asunto(s)
Córnea/patología , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/genética , Progresión de la Enfermedad , Humanos , Fenotipo , Factores de TiempoRESUMEN
The cornea is precious to sight. Its intricate cellular arrangement and physiology enable it to be transparent and refractive. Corneal dystrophies (CDs) impact vision at various decades of life depending on the dystrophy at hand. Left untreated, visual ramifications ensue. This review article will summarize the current knowledge of the various CDs and the relatively controversial classification based on new genetic knowledge and clinical and histological characteristics. The application of contact lenses, both soft and rigid, has a place in the care and rehabilitation of these unique corneas.
Asunto(s)
Lentes de Contacto , Distrofias Hereditarias de la Córnea/terapia , Córnea/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Humanos , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: We aimed to explore a new classification system based on the change of focal corneal curvatures and corneal thickness in Terrien's corneal degeneration with optical coherence tomography. METHODS: This was a cross-sectional study. Ninety eyes of 59 patients with Terrien's degeneration were examined with slit lamp biomicroscopy, Orbscan II corneal tomography and the Visante OCT system, and were staged according to Süveges's classification. RESULTS: The ratio of female to male patients was 1.57:1. The ratio of bilateral to unilateral lesions was 1.27:1. The occurrence of bilateral lesion was higher in males than in females (x(2) = 7.791, p = 0.005). There was no difference in the mean age between female and male patients (t = 1.859, p = 0.068), or between patients with bilateral and unilateral lesions (t = 1.797, p = 0.078).The minimum corneal thickness at the thinnest point (MinCT) and anterior curvature of the peripheral cornea were almost normal in the initial stages of disease. The anterior curvature was flattened when MinCT became less than 0.56 mm, returned to normal when MinCT was no more than 0.24 mm, and bowed forward when MinCT was no more than 0.13 mm. The posterior corneal curvatures were bowed forward from their normal curvatures in 42 of 90 eyes when MinCT was no more than 0.41 mm. These eyes' MinCT ranged from 0 to 0.41 mm. There was a strong correlation between change of corneal curvatures and MinCT (r = -0.943, p < 0.01). A new classification of six stages based on corneal curvatures is proposed for evaluating the development of Terrien's degeneration. Statistically, there was a moderate correlation between either the Süveges staging or the new staging and the width and circumference of corneal lesions, visual acuity, and simulated keratometric value (all r < 0.6). The correlation of MinCT with the new classification based on corneal curvatures was higher than that with Süveges's classification (r 1 vs. r 2 , -0.943 vs. -0.801). CONCLUSION: The proposed new classification based on focal corneal curvatures is closely associated with corneal thinning, is valuable for evaluating the development of Terrien's degeneration and may enhance surgical planning.
Asunto(s)
Córnea/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Tomografía de Coherencia Óptica , Adolescente , Adulto , Anciano , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Lámpara de Hendidura , Agudeza VisualRESUMEN
PURPOSE: To characterize Bietti crystalline dystrophy (BCD) in different stages using multiple imaging modalities. METHODS: Sixteen participants clinically diagnosed as BCD were included in the retrospective study and were categorized into 3 stages according to fundus photography. Eleven patients were genetically confirmed. Fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging features of BCD were analyzed. RESULTS: On fundus autofluorescence, the abnormal autofluorescence was shown to enlarge in area and decrease in intensity with stages. Using spectral domain optical coherence tomography, the abnormalities in Stage 1 were observed to localize in outer retinal layers, whereas in Stage 2 and Stage 3, more extensive retinal atrophy was seen. In enhanced depth imaging, the subfoveal choroidal layers were delineated clearly in Stage 1; in Stage 2, destructions were primarily found in the choriocapillaris with associated alterations in the outer vessels; Stage 3 BCD displayed severe choroidal thinning. Choroidal neovascularization and macular edema were exhibited with high incidence. IVS6-8del17bp/inGC of the CYP4V2 gene was the most common mutant allele. CONCLUSION: Noninvasive fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging may help to characterize the chorioretinal pathology of BCD at different degrees, and therefore, we propose staging of BCD depending on those methods. Physicians should be cautious of the vision-threatening complications of the disease.
Asunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Imagen Multimodal , Enfermedades de la Retina/clasificación , Enfermedades de la Retina/diagnóstico , Adulto , Atrofia , Neovascularización Coroidal/patología , Distrofias Hereditarias de la Córnea/genética , Sistema Enzimático del Citocromo P-450/genética , Familia 4 del Citocromo P450 , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Imagen Óptica , Retina/patología , Enfermedades de la Retina/genética , Drusas Retinianas/patología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: This report suggests how corneal dystrophies (CDs) should be diagnosed at the slit lamp and specifies the new IC(3)D classification of CDs in 2015 which incorporates new information. METHODS: IC(3)D reviewed all peer-reviewed articles on CDs 2008 to 6/2014. Corneal dystrophy templates and anatomic classifications were updated. RESULTS: To detect landmarks for correct classification of CDs, opacity patterns and opacity units are determined at the slit lamp. Opacity patterns are described as (1) horizontal extension, (2) vertical extension ("depth") and clarity of the (3) cornea in between. Horizontal extension is assessed using a broad beam, vertical extension using a bright, thin slit lamp beam in high magnification. For assessment of opacity units, examination using retroillumination with dilated pupil is indispensable! This is especially true for epithelial and endothelial CDs. With a better review of the cellular origin of CDs, a new anatomic classification is proposed: 1. epithelial and subepithelial; 2. epithelial-stromal transforming growth factor beta-induced (TGFBI); 3. stromal; 4. endothelial dystrophies. Epithelial recurrent erosion dystrophies include three epithelial dystrophies (Franceschetti CD, dystrophia Smolandiensis, and dystrophia Helsinglandica) and are differentiated against TGFBI dystrophies, also associated with recurrent epithelial erosion. The chromosome locus of Thiel-Behnke CD is only located on 5q31. The entity previously called Thiel-Behnke on chromosome 10q24 may be a unique corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is an autosomal recessive disorder. The autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to be a unique entity and most cases appear to be similar to other reported dystrophies, particularly posterior polymorphous corneal dystrophy (PPCD). CONCLUSIONS: The 2015 revision of IC(3)D classification includes an updated anatomic classification more accurately describing TGFBI dystrophies to affect multiple layers. Some entities, e.g., Grayson Wilbrandt, Meretoja syndrome, and CHED2 are removed. All authors and reviewers should adhere to this classification of CDs!
Asunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Pruebas Genéticas/normas , Clasificación Internacional de Enfermedades/normas , Guías de Práctica Clínica como Asunto , Lámpara de Hendidura/normas , Distrofias Hereditarias de la Córnea/genética , Marcadores Genéticos/genética , Alemania , Humanos , Clasificación Internacional de Enfermedades/tendenciasRESUMEN
PURPOSE: The purpose of this case report is to review granular corneal dystrophy (GCD) and examine the new paradigm in its classification and treatment. CASE REPORT: A 49-year-old white male patient reported yearly for monitoring of GCD. He had an ocular surgical history in the left eye for penetrating keratoplasty in 1989 and phototherapeutic keratectomy with mitomycin C for graft recurrence of stromal bread-crumb opacities 17+ years later in 2002. At his last examination, the patient's vision and comfort was stable in each eye, with minimal recurrence of granular opacities in the left surgical eye, stable granular opacities in the right eye, no recurrent corneal erosion symptoms in either eye, and best spectacle-corrected vision of 20/40 OD and 20/30 OS. CONCLUSIONS: GCD is a Category 1, Stromal, TGFBI-associated corneal dystrophy. Although it is classified as a stromal dystrophy, research suggests the possibility that the granular opacities have an origination to the corneal epithelium with a migratory effect to the corneal stroma. Patients with Groenouw I, like the one in this report, usually do not have severely compromised vision. When vision is significantly affected or recurrent corneal erosion occurs, despite first- and second-line treatments, viable management options thereafter include photokeratectomy and other new surgical treatments such as femtosecond deep anterior lamellar keratoplasty and femtosecond laser-assisted keratoplasty. Future advancements in diagnostic technology, immunohistologic and genetic testing, medications, and surgery will allow for advancements in treating and managing patients with GCD.
Asunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/cirugía , Queratectomía Fotorrefractiva , Distrofias Hereditarias de la Córnea/diagnóstico , Sustancia Propia/cirugía , Topografía de la Córnea , Humanos , Queratoplastia Penetrante , Masculino , Persona de Mediana Edad , Recurrencia , Agudeza Visual/fisiologíaRESUMEN
Many of the corneal dystrophies have now been genetically characterized, and a system was established in 2008 by The International Committee for Classification of Corneal Dystrophies (IC3D) in an attempt to standardize the nomenclature. IC3D provided a classification system whereby all dystrophies can be categorized on the basis of the underlying genetic knowledge. Since that time, further work has established even more phenotypic and allelic heterogeneity than anticipated, particular for Fuchs endothelial corneal dystrophy and posterior polymorphous dystrophy. Using genome-wide association studies, a number of genes are now implicated both in normal corneal quantitative traits, such as central corneal thickness, as well as in disease. There is also a trend towards functional characterization of the genetic variants involved to elucidate the pathophysiology of these entities. This review article will provide an overview of the knowledge to date, with an emphasis on findings since the IC3D classification was published in 2008.
Asunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/genética , Biología Molecular/clasificación , Estudio de Asociación del Genoma Completo , Humanos , Clasificación Internacional de Enfermedades , Terminología como AsuntoRESUMEN
In this review we summarise the new insights into corneal dystrophies following publication of the IC3D classification in 2008. Topics covered are new mutations, new clinical/histological phenotypes, first descriptions of known mutations in previously not mentioned ethnic groups, new dystrophic entities after modern corneal surgery and potentially new types of conservative therapy.
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Distrofias Hereditarias de la Córnea/clasificación , Clasificación Internacional de Enfermedades , Lámina Limitante Anterior/patología , Distrofias Hereditarias de la Córnea/genética , Distrofias Hereditarias de la Córnea/patología , Distrofias Hereditarias de la Córnea/terapia , Sustancia Propia/patología , Análisis Mutacional de ADN , Diagnóstico Diferencial , Endotelio Corneal/patología , Humanos , FenotipoRESUMEN
Macular corneal dystrophy (MCD; MIM 217800) is an autosomal recessive hereditary disease in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantation. MCD is classified into two subtypes, type I and type II, defined by the respective absence and presence of sulphated keratan sulphate in the patient serum, although both types have clinically indistinguishable phenotypes. The gene responsible for MCD type I has been mapped to chromosome 16q22, and that responsible for MCD type II may involve the same locus. Here we identify a new carbohydrate sulphotransferase gene (CHST6), encoding an enzyme designated corneal N-acetylglucosamine-6-sulphotransferase (C-GlcNAc6ST), within the critical region of MCD type I. In MCD type I, we identified several mutations that may lead to inactivation of C-GlcNAc6ST within the coding region of CHST6. In MCD type II, we found large deletions and/or replacements caused by homologous recombination in the upstream region of CHST6. In situ hybridization analysis did not detect CHST6 transcripts in corneal epithelium in an MCD type II patient, suggesting that the mutations found in type II lead to loss of cornea-specific expression of CHST6.
Asunto(s)
Cromosomas Humanos Par 16 , Distrofias Hereditarias de la Córnea/genética , Mutación , Sulfotransferasas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/enzimología , Etiquetas de Secuencia Expresada , Femenino , Marcadores Genéticos , Humanos , Sulfato de Queratano/sangre , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Sulfotransferasas/química , Carbohidrato SulfotransferasasRESUMEN
PURPOSE: To investigate the clinical and genetic features of Korean patients with corneal dystrophies associated with mutations in the human transforming growth factor-ß-induced (TGFBI) gene. METHODS: In this study, 387 subjects (71 families and 89 individuals - 268 patients having TGFBI corneal dystrophies and 119 normal relatives) were assessed. All subjects underwent a complete ophthalmologic evaluation, including biomicroscopic inspection and dilated fundus examination. As a control, 100 individuals without corneal disease were selected from the general population. The polymerase chain reaction (PCR) and direct sequencing were used to screen for mutations in TGFBI. RESULTS: All subjects recruited exhibited a range of corneal dystrophies, including Thiel-Behnke corneal dystrophy (TBCD, R555Q; 6 families and 4 individuals), granular corneal dystrophy type 2 (GCD2, R124H; 61 families and 80 individuals), lattice corneal dystrophy (LCD; 4 families and 5 individuals; 7 with type 1 [R124C], and 2 with a variant [L527R, P542R]). The disease showed an autosomal dominant inheritance pattern in all families. CONCLUSIONS: R124H in GCD2 was the most common mutation. GCD1 and Reis-Bucklers corneal dystrophy were not found. In the GCD2 patients there were a large number of laser refractive surgery-induced corneal opacities. A spontaneous R124H mutation was confirmed in an already mutated allele that resulted in a change from a heterozygous into a homozygous form. Also, a novel mutation, P527R, was identified in LCD.
Asunto(s)
Pueblo Asiatico , Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Factor de Crecimiento Transformador beta/genética , Adulto , Anciano , Secuencia de Bases , Estudios de Casos y Controles , Niño , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/epidemiología , Femenino , Genes Dominantes , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la Polimerasa , República de Corea/epidemiología , Análisis de Secuencia de ADNRESUMEN
PURPOSE: Investigate the genotype-phenotype correlations for five TGFBI (transforming growth factor, beta-induced) mutations including one novel pathogenic variant and one complex allele affecting the fourth FAS1 domain of keratoepithelin, and their potential effects on the protein's structure. METHODS: Three unrelated families were clinically diagnosed with lattice corneal dystrophy (CD) and one with an unclassified CD of Bowman's layer. Mutations in the TGFBI gene were detected by direct sequencing, and the functional impact of each variant was predicted using in silico algorithms. Corneal phenotypes, including histological examinations, were compared with the literature data. Furthermore, molecular modeling studies of these mutations were performed. RESULTS: Two distinct missense mutations affecting the same residue at position 509 of keratoepithelin: p.Leu509Pro (c.1526T>C) and p.Leu509Arg (c.1526T>G) were found to be associated with a lattice-type CD. The novel p.Val613Gly (c.1828T>G) TGFBI mutation was found in a sporadic case of an Algerian individual affected by lattice CD. Finally, the Bowman's layer CD was linked to the association in cis of the p.Met502Val and p.Arg555Gln variants, leading to the reclassification of this CD as atypical Thiel-Behnke CD. Structural modeling of these TGFBI mutations argues in favor of these mutations being responsible for instability and/or incorrect folding of keratoepithelin, predictions that are compatible with the clinical diagnoses. CONCLUSIONS: Description of a novel TGFBI mutation and a complex TGFBI allele further extends the mutational spectrum of TGFBI. Moreover, we show convincing evidence that TGFBI mutations affecting Leu509 are linked to the lattice phenotype in two unrelated French families, contrasting with findings previously reported. The p.Leu509Pro was reported to be associated with both amyloid and non-amyloid aggregates, whereas p.Leu509Arg has been described as being responsible for Epithelial Basement Membrane Dystrophy (EBMD).
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Lámina Limitante Anterior/metabolismo , Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Factor de Crecimiento Transformador beta/genética , Adulto , Anciano de 80 o más Años , Argelia/etnología , Alelos , Secuencia de Aminoácidos , Lámina Limitante Anterior/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/epidemiología , Distrofias Hereditarias de la Córnea/etnología , Distrofias Hereditarias de la Córnea/patología , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Francia/epidemiología , Frecuencia de los Genes , Estudios de Asociación Genética , Ligamiento Genético , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Linaje , Fenotipo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d .
Asunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/genética , Técnicas de Diagnóstico Oftalmológico , Pruebas Genéticas/métodos , Clasificación Internacional de Enfermedades , Terminología como Asunto , Distrofias Hereditarias de la Córnea/diagnóstico , HumanosAsunto(s)
Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/genética , Factor de Crecimiento Transformador beta/genética , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/terapia , Análisis Mutacional de ADN , Alemania , Humanos , Clasificación Internacional de Enfermedades , Fenotipo , Lámpara de HendiduraRESUMEN
PURPOSE: To report a possible case of phenotypic non-penetrance in granular corneal dystrophy type II (GCD-II). METHODS: DNA analysis was performed on 11 patients with white granular corneal opacities and 50 normal controls after informed consent was obtained. The TGFBI gene was analyzed by sequencing DNA from epidermal keratinocytes obtained using adhesive tape. RESULTS: The heterozygous R124H mutation of TGFBI gene was found in all 11 patients. Although 49 normal controls had no mutation in the TGFBI gene, one normal control, a 26-year-old man, had the heterozygous R124H mutation of TGFBI gene. His 55-year-old father had the same mutation, but no corneal opacities. CONCLUSION: As not all mutations are expressed in the phenotype, GCD-II gene mutation may have non-penetrance. This report documents a possible case of phenotypic non-penetrance in GCD-II.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Penetrancia , Fenotipo , Adulto , Arginina , Secuencia de Bases , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/patología , Opacidad de la Córnea/etiología , Opacidad de la Córnea/genética , Epidermis/metabolismo , Epidermis/patología , Proteínas de la Matriz Extracelular/genética , Heterocigoto , Histidina , Humanos , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Mutación Missense , Factor de Crecimiento Transformador beta/genéticaRESUMEN
AIMS: To evaluate mutations in the transforming-growth-factor-beta-induced (TGFBI) gene in patients of Czech origin with autosomal dominant corneal dystrophies. METHODS: The coding sequence of the TGFBI gene was analysed in 22 affected Czech individuals from 7 apparently unrelated families. Comparison of phenotype to genotype was performed. RESULTS: A H626P mutation, previously only described in a family with a variant of lattice corneal dystrophy (LCD), was detected in one family with superficial geographic corneal opacities. Light microscopy of 2 samples obtained following either a prior superficial keratectomy or keratoplasty showed amyloid but no fuchsinophilic deposits. In a family with LCD type I, an R124C mutation was identified. The R124L mutation was shown to be causative of Reis-Bucklers corneal dystrophy in 2 families. A family with Thiel-Behnke corneal dystrophy exhibited an R555Q mutation. In 2 families with granular corneal dystrophy type I, the typical R555W change was identified. CONCLUSION: The phenotype of the family with the H626P mutation differed from the phenotype previously reported for this change.
Asunto(s)
Catarata/genética , Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Factor de Crecimiento Transformador beta/genética , Adulto , Amiloide/metabolismo , Catarata/metabolismo , Catarata/patología , Córnea/metabolismo , Córnea/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/metabolismo , República Checa , Femenino , Histidina , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , ProlinaRESUMEN
The International Committee on Classification of Corneal Dystrophies, briefly IC (3)D, was founded with the sponsorship of the American Cornea Society and the American Academy of Ophthalmology in July 2005. This committee consists of 17 corneal experts (1) from USA, Asia and Europe. The goal of this group was to develop a new, internationally accepted classification of corneal dystrophies (CD) based on modern clinical, histological and genetical knowledge. The aim of the new classification should be to avoid wrong interpretations and misnomers of the different forms of CD. The IC (3)D extensive manuscript is in press as Supplement publication in the journal "Cornea". The 25 different CD are divided in four categories by clinical and genetical knowledge. Additionally, templates for each type of CD are included. Finally, many typical color slit-lamp photos are presented in the publication together with essential references and current genetical results in tabular form. As members of IC (3)D the authors present a clinical landmark survey of the different corneal dystrophies. The ophthalmologist is the first to examine and to diagnose a new patient with a probable CD at the slit-lamp. Our elaborated table of landmarks is supposed to be a "bridge" for the ophthalmologist to precisely define the corneal opacities of a presumed CD. This "bridge" makes it easier for them to study the IC (3)D Supplement publication and to get more information including adequate differential diagnosis.
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Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Clasificación Internacional de Enfermedades , Terminología como Asunto , Distrofias Hereditarias de la Córnea/genética , Diagnóstico Diferencial , HumanosAsunto(s)
Enfermedades de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/diagnóstico , Epitelio Corneal/patología , Córnea/patología , Enfermedades de la Córnea/clasificación , Enfermedades de la Córnea/genética , Enfermedades de la Córnea/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/genética , Distrofias Hereditarias de la Córnea/patología , Diagnóstico Diferencial , Diagnóstico Precoz , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , HumanosRESUMEN
PURPOSE: To identify mutations in the Transforming Growth Factor Beta Induced (TGFBI) gene in Hungarian patients with corneal dystrophy and to characterize histological features of their corneal buttons excised during penetrating keratoplasty. METHODS: Exons of TGFBI were sequenced in 38 members of 15 unrelated families with corneal dystrophy and exon 12 was also sequenced in 100 healthy controls from the same population. Immunohistological analysis of available corneal buttons excised during penetrating keratoplasty was also performed. RESULTS: Molecular genetic analysis revealed a heterozygous R124C mutation in 18 patients with lattice type I dystrophy. A R555W heterozygous mutation was detected in five patients with granular Groenouw type I corneal dystrophy and a R555Q heterozygous mutation was found in four patients clinically diagnosed with Reis-Bücklers (one patient) and Thiel-Behnke (three patients) dystrophy. Three patients with "atypical granular" dystrophy later diagnosed as Avellino dystrophy were heterozygous for the R124H mutation. A novel heterozygous mutation (T1640C) causing a F547S amino acid exchange was detected in a patient with polymorphic corneal amyloidosis. Immunohistochemistry showed the presence of BIGH3 protein deposits in all examined corneal buttons. Electron microscopy confirmed the presence of amyloid fibrils in the case of the novel mutation. CONCLUSIONS: Our results indicate that molecular genetic analysis is required to confirm the diagnosis of corneal dystrophies. We report the first cases of Avellino dystrophy from Central-Eastern Europe. We conclude that the novel F547S mutation causes polymorphic corneal amyloidosis since no other mutations were detected in the TGFBI gene of this patient and the novel mutation could not be found in healthy controls.
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Amiloidosis/genética , Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Fenilalanina , Serina , Factor de Crecimiento Transformador beta/genética , Sustitución de Aminoácidos , Amiloidosis/patología , Amiloidosis/cirugía , Secuencia de Bases , Córnea/patología , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/patología , Distrofias Hereditarias de la Córnea/cirugía , Heterocigoto , Humanos , Hungría , Queratoplastia Penetrante , Persona de Mediana EdadRESUMEN
Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09 % of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. Practically, the ophthalmologist manages functional symptoms, such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care.
Asunto(s)
Enfermedades de la Córnea , Síndrome de Cogan/clasificación , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/terapia , Enfermedades de la Córnea/clasificación , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/etiología , Enfermedades de la Córnea/terapia , Distrofias Hereditarias de la Córnea/clasificación , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/terapia , Diagnóstico Diferencial , Humanos , Queratoplastia Penetrante , Láseres de Excímeros , Queratectomía FotorrefractivaRESUMEN
Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09% of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. In practice, the ophthalmologist manages functional symptoms such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care.