[The cornea as an indicator for systemic diseases]. / Die Hornhaut als Indikator für Systemerkrankungen.

Numerous systemic diseases can be manifested at the cornea. Sometimes the corneal involvement is the first sign of the systemic process. It may be manifested in many different forms, such as an ulcer in the corneal periphery or a crystalline keratopathy. Therapy is interdisciplinary and primarily directed against the underlying disease.

[Paraproteinemic Keratopathy as a Clinical Sign of Monoclonal Gammopathy]. / Paraproteinämische Keratopathie als klinisches Zeichen einer monoklonalen Gammopathie.

Patients with monoclonal gammopathy can show paraproteinemic keratopathy (PPK) with an indication to treatment. PPK has to be differentiated from corneal dystrophies, systemic metabolic disorders with corneal involvement, as well as from immunologic and inflammatory corneal diseases.

Recurrence of paraproteinemic keratopathy after penetrating keratoplasty and its assessment with confocal microscopy.

PURPOSE: To report on a case of recurrence of paraproteinemic keratopathy (PPK) associated with monoclonal gammopathy after bilateral penetrating keratoplasty. OBSERVATIONS: Penetrating keratoplasty was performed on both eyes of a 45-year-old man due to bilateral progressive corneal stromal clouding. Recurrence of the corneal stromal opacities accompanied by a decrease in visual acuity was observed on slit-lamp examination already two years after penetrating keratoplasty. Confocal laser scanning microscopy (CLSM) of the corneal grafts performed three years after penetrating keratoplasty showed bilateral morphological changes identical to that found in the patient's corneas prior to penetrating keratoplasty. A hematological work-up revealed monoclonal gammopathy of type IgG kappa. The histochemical examination of the explanted corneas confirmed the diagnosis of PPK. CONCLUSIONS AND IMPORTANCE: Paraproteinemic keratopathy is an underdiagnosed ophthalmological condition, which may be associated with potentially life-threatening hematologic disorders. A hematological workup should be performed in patients with corneal opacities of uncertain etiology. Penetrating keratoplasty should be performed with caution in patients with monoclonal gammopathy due to the possibility of a very fast recurrence of PPK in the corneal graft. This is the first presentation of the recurrence of flake-like PPK after penetrating keratoplasty assessed with CLSM.

[The cornea as an indicator for systemic diseases]. / Die Hornhaut als Indikator für Systemerkrankungen.

Numerous systemic diseases can be manifested at the cornea. Sometimes the corneal involvement is the first sign of the systemic process. It may be manifested in many different forms, such as an ulcer in the corneal periphery or a crystalline keratopathy. Therapy is interdisciplinary and primarily directed against the underlying disease.

[Hematological diagnosis in the corneal consultation]. / Hämatologische Diagnose in der Hornhautsprechstunde.

This case report describes a diagnostic chain in a patient with atypical bilateral corneal opacity, which led to the diagnosis of a hematological disorder. The patient's medical history, clinical appearance and findings in confocal microscopy gave rise to the suspicion of a paraproteinemic keratopathy. The hematological laboratory diagnostics revealed a monoclonal gammopathy of the IgG kappa type. The bone marrow puncture led to the diagnosis of a lymphoplasmacytic lymphoma, which belongs to the group of B­cell non-Hodgkin's lymphomas. This case demonstrates that paraproteinemic keratopathy can be associated with potentially life-threatening hematological diseases.

[The revised newest IC³D classification of corneal dystrophies]. / Die revidierte neueste IC³D-Klassifikation der Hornhautdystrophien.

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!

[Therapy for systemic metabolic disorders based on the detection of basic corneal landmarks in childhood]. / Hornhaut-Schlüsselbefunde im Kindesalter als Hinweis für therapierbare systemische Stoffwechselerkrankungen.

Many systemic lysosomal storage disorders show basic corneal opacities already in childhood. The lysosome is a cell organelle, produced by Golgi's apparatus, that is surrounded by a membrane and contains hydrolytic enzymes that break down food molecules, especially proteins and other complex molecules. The ophthalmologist's precise diagnosis of corneal clouding at the slit-lamp may reveal the correct interpretation of the specific lysosomal storage disorder. It is very important to diagnose such diseases as soon as possible because today the development of systemic enzymatic therapies has broadened the therapeutic armamentarium for the current standard of care. The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabry's disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischer's ring in Wilson's disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). Enzyme replacement therapy is currently indicated for MPS I, MPS II, and MPS VI, haematopoietic stem cell transplantation; painful, bilateral pseudo-dendritic opacities in tyrosinemia type II (eponym: Richner-Hanhart syndrome), low phenylalanine and tyrosine diet result in complete disappearance of corneal alterations with a consecutive painfree period. Strict diet during the whole life is necessary to prevent corneal recurrences and the occurrence of palmo-plantar keratoses. Such therapies can enable the patient to lead an otherwise normal life for decades.

[Corneal dystrophy (CD)-induced pain and visual impairment in childhood]. / Hornhautdystrophie-(HD-)bedingte Schmerzen und Visusbeeinträchtigung im Kindesalter.

Many forms of the 25 corneal dystrophies (CD) manifest already in childhood with bilateral corneal opacities without any visual impairment in most cases. Pain attacks due to recurrent erosion with red eye and epiphora can occur in combination with the first dystrophy-specific corneal opacities, e.g., nest-like lattice lines + corneal erosion in lattice CD. Often we can observe a joint occurrence. The parents accompany their child to consult the ophthalmologist concerning the recurrent and joint pain attacks. The ophthalmologist can also diagnose in such a situation subtle corneal opacities on the painless, contralateral eye, e.g., those of lattice, granular, macular or Reis-Bücklers CD. The correct interpretation of this combination does not lead the ophthalmologist to an inflammatory-, but to a dystrophy-induced interpretation of this entity. In a further group of CD, e.g., in Franceschetti CD, the typical history of this entity is a dominant disorder with recurrent epithelial erosions starting in the first decade, declining in frequency and severity at a later age, and associated with a central, disk-like haze of the subepithelial cornea from middle age. The recurrent erosions in childhood lasted 3-5 days and were followed by complete recovery. Congenital corneal clouding in the form of a milky ground-glass appearance can be observed in the rare endothelial CD, such as in congenital hereditary endothelial dystrophy 1 and 2 (CHED 1 and 2), X-linked endothelial CD (XECD), and in posterior polymorphous CD (PPCD). The differential diagnosis for congenital glaucoma is of essential importance. The parents of babies with congenital corneal opacification should be examined at the slit-lamp to in- or exclude the appearance of mooncrater-like endothelial changes.

[Discrete bilateral corneal deposits in a young woman]. / Diskrete bilaterale korneale Ablagerungen bei einer jungen Frau.

A 17-year-old asymptomatic girl presented with discrete bilateral deposits in the superficial corneal stroma. The diagnosis of very early and in this form as yet undescribed manifestation of Schnyder's corneal dystrophy, was only possible based on the family history.

[Endothelial corneal dystrophies (CD) - diagnosis and therapy]. / Endotheliale Hornhautdystrophien (HD) - Diagnose und Therapie.

Clinical, histological, and genetic definitions of the four endothelial corneal dystrophies (CD) are presented. Of these, Fuchs endothelial CD is one of the most common corneal dystrophies in Europe and North America. Beside bullous keratopathy, Fuchs CD represents the most frequent indication for posterior lamellar keratoplasty that is currently termed "Descemet stripping endothelial keratoplasty" or abbreviated, "DSEK". A comparison of the advantages and disadvantages of DSEK against the established Excimer laser-assisted penetrating keratoplasty is given. The often simultaneous occurrence of Fuchs CD and cataract should be treated by phacoemulsification and implantation of a posterior chamber lens before the keratoplasty. There are many comparative studies concerning the different surgical techniques to evaluate their intra- and postoperative advantages and results. Many years will be necessary before we can get a scientific and definitive assessment.

[New international classification of corneal dystrophies (CD)]. / Neue internationale Klassifikation der Hornhautdystrophien.

The Cornea Society founded an international committee of 17 corneal experts from the USA, Asia and Europe in 2005. The goal of this group was to develop a new international classification of corneal dystrophies (CD) based on modern clinical, histological and genetic knowledge. Both authors are members of this committee. The elaboration of the classification included the correction of many misinterpretations with regard to the different forms of CD which were published in the past literature. In spite of important results concerning the genetic locus and identification of genes and mutations, corneal dystrophies are typically classified with respect to the level of the cornea that is involved. An accurate and up-to-date template for each form of the 25 CDs was created that included the current clinical, histological and genetic information. To indicate the level of evidence supporting the existence of a given dystrophy, the CDs are divided into four different categories. The new international classification of CDs was published in English, Spanish and German as a 40 page supplement with 64 figures, mostly in color. A more detailed description of genetic mutations is included in the appendix.

[Bilateral disc-like corneal opacity before cataract extraction]. / Seitengleiche, scheibenförmige Hornhauttrübung vor Kataraktextraktion.

An 81-year-old patient presented for cataract extraction of the right eye. In addition a bilateral disc-like corneal opacity was present which was classified as central cloudy corneal dystrophy of François. This rare and clinically unproblematic condition will be discussed.

[Masquerade keratitis due to hereditary corneal disorders]. / Maskerade-Keratitis bei erblichen Hornhauterkrankungen.

Hereditary corneal disorders can show a unilateral corneal erosion for several days due to different morphological etiologies which may result in the misdiagnosis of bacterial or viral keratitis. In such a situation it is very important to examine the contralateral eye with regard to a possible corneal opacity. The slit lamp examination has to be performed with dilated pupil in direct and indirect illumination. Patient history including familial ocular problems and recurrent alternating ocular pain can be a hint for the correct diagnosis. Masquerade keratitis of hereditary corneal disorders can be distinguished in 3 main groups: (i) recurrent corneal erosion due to systemic hereditary disorders with corneal involvement; (ii) recurrent corneal erosion due to corneal dystrophies with dystrophy-specific corneal opacities; (iii) recurrent corneal erosion in childhood without dystrophy-specific corneal opacities (occurrence of dystrophy-specific corneal opacities in adults). The ocular pain which may last several days with third group of patients often occurs in the second half of night. The children's suffering is enormous and has a negative impact on the whole family. The wearing of therapeutic contact lenses during the night may considerably reduce the ocular pain.

[The IC3D classification of the corneal dystrophies]. / IC3D-Klassifikation von Hornhautdystrophien.

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 .

[New international classification of corneal dystrophies and clinical landmarks]. / Neue internationale Klassifikation der Hornhautdystrophien und klinische "Schlüsselbefunde".

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.