[Hereditary Macular Dystrophies]. / Hereditäre Makuladystrophien.

Hereditary macular dystrophies are part of the group of inherited retinopathies caused by mutations of specific genes. Challenging features are their rarity, enormous clinical and genetic heterogeneity, unspecific visual disturbances, and often only mild initial fundus changes. The onset of macular dystrophies may occur at any age. They manifest in the macular region, whereas fundus changes can reach the mid periphery as well. In some cases, macular dystrophy can progress into generalised retinal dystrophy, depending on the severity of the causative mutations. Funduscopy alone is often insufficient for diagnosis. However, correct diagnosis is essential for the patient for counseling, low vision aids, support, and therapeutic options. Retinal imaging, with fundus autofluorescence, near-infrared autofluorescence and optical coherence tomography, is very important, as it can show typical changes not visible on funduscopy. In cases where morphological changes are absent, retinal dysfunction must be detected by electrophysiological testing. There has been technical progress in molecular genetic testing in recent years. With the development of modern sequencing, an analysis for all known genes of hereditary retinal dystrophies has been established. The genetic defect can now be identified in more cases than before. However, a correct initial clinical diagnosis is still required for successful genetic analysis. The importance of a genetically confirmed diagnosis is increasing, as this is needed for patients who could have the chance in the near future to participate in therapeutic trials.

[Hereditary macular dystrophies in differential diagnosis of AMD]. / Hereditäre Makuladystrophien in der Differenzialdiagnose der AMD.

The onset of hereditary macular dystrophies may occur at all ages and may be the origin of visual disturbances even after the age of 50 years. During the disease course, many macular dystrophies change their fundus appearance, finally leading to a geographic chorioretinal atrophy making it difficult to distinguish the disease form dry AMD. Furthermore, a macular dystrophy associated CNV may be misleading to the diagnosis of wet AMD. Additional fundus autofluorescence and optical coherence tomography imaging are very valuable for delineating macular dystrophies from AMD. In this paper we provide an overview of the important hereditary macular dystrophies which should be considered as differential diagnoses for AMD.

[Combined retinal artery and vein occlusions associated with interferon beta therapy]. / Kombinierter retinaler arteriovenöser Verschluss unter Interferon-ß-Therapie.

Interferon (IFN) beta is commonly used in the treatment of multiple sclerosis. Thromboembolic complications may be associated with this therapy. We describe a case of branch arterial occlusions combined with central vein occlusion in a female patient who had undergone IFN beta therapy for 10 years. Thromboembolic and cardiovascular risk factors responsible for this event were excluded. The appearance of retinal vein and artery occlusions in our patient indicates an association with the long-term use of IFN beta.

[Dry eye syndrome and neurotrophic keratitis in childhood. Causes and therapy]. / Keratoconjunctivitis sicca und neurotrophe Keratopathie im Kindesalter. Ursachen und Therapie.

PURPOSE: The purpose of this review is to enhance the physician's awareness of dry eye syndrome and neurotrophic keratitis in children, to describe the most frequently associated conditions and to discuss the diagnostic and therapeutic options available. METHODS: A literature review of the pathogenesis of dry eye syndrome and neurotrophic keratitis in children was carried out, clinical cases from our pediatric ophthalmology office are presented as well as therapeutic strategies. RESULTS: Diseases of the cornea and ocular surface such as dry eye syndrome, neurotrophic keratitis and corneal ulcers are infrequent in children compared to adults. However, they do occur and should be diagnosed and treated as soon as possible in order to prevent long-term complications and amblyopia. CONCLUSIONS: Inflammatory diseases of the ocular surface can be easily overlooked in children due to the often unknown spectrum of differential diagnoses and the frequently reduced cooperation during examination of young children. Correct and early diagnosis is essential for prevention of long-term complications, e.g. corneal ulceration and scarring.

[Evidence-based diagnostic approach to inherited retinal dystrophies 2009]. / Evidenzbasierte Diagnostik hereditärer Netzhautdystrophien 2009.

BACKGROUND: Hereditary retinal dystrophies comprise a heterogeneous group of inherited retinal disorders with variable clinical presentation and multiple associated genes. Clinical diagnosis and differential diagnosis are difficult. The purpose of the current paper is to provide guidelines for an effective diagnostic approach. METHODS: A literature search was carried out and our own data on clinical (n = 3200) and molecular genetic (n = 4050) diagnosis of patients with retinal dystrophies were evaluated. RESULTS: For an early diagnosis it is of importance to include inherited retinal dystrophies in the differential diagnosis of unexplained visual disturbances. The most important clinical test is the full-field electroretinogram (ERG), which allows detection or exclusion of generalised retinal dystrophies. If the full-field ERG is normal, a multifocal ERG will distinguish macular dystrophies. Fundus autofluorescence, near-infrared autofluorescence and high resolution optical coherence tomography improve the early diagnosis because morphological alterations can be detected prior to their ophthalmoscopic visibility. In addition, these non-invasive imaging techniques reveal new phenomena which are important for the differential diagnosis and follow-up of retinal dystrophies as well as for an improved understanding of their pathogenesis. Routine molecular genetic diagnosis is available for an increasing number of retinal dystrophies. A succinct clinical diagnosis is a prerequisite to allow selection of the gene(s) to be analysed. If genetic testing is indicated, a human geneticist should be involved for counselling of the patient and possibly further family members and initiation of the necessary steps for DNA testing. CONCLUSION: The combination of electrophysiological testing, retinal imaging and molecular genetic analysis allows a differentiated diagnosis of inherited retinal dystrophies and an individual counselling of patients. If inherited retinal dystrophies are suspected, a detailed examination in a retinal centre specialised on inherited retinal dystrophies is recommended.

[Clinical manifestations of functional disturbances of the retinal pigment epithelium]. / Klinische Manifestationen von Funktionsstörungen des retinalen Pigmentepithels.

The retinal pigment epithelium (RPE) serves a variety of different functions and impairment of these functions can lead to a multitude of different diseases of the posterior segment of the eye. The RPE plays an important role as an ion and fluid pump for the reabsorption of subretinal fluid in retinal detachment. On the other hand, defects in this pump function and in the outer blood-retinal barrier formed by the RPE, lead to fluid retention in inflammatory diseases. Metaplasia of RPE cells to myofibroblasts can lead to proliferative vitreoretinopathy and tractive retinal detachment. Early age-related maculopathy is caused by disturbances of phagocytosis and metabolism of the RPE. Imbalance of the physiological equilibrium between vasoproliferative and vasoinhibitory factors secreted by the RPE is probably involved in the development of atrophic or neovascular forms of advanced age-related macular degeneration. Mutations in the different steps involved in regeneration of the visual pigment (visual cycle) may lead to retinal dystrophy. Finally, immunoregulatory properties of the RPE are responsible for the phenomenon of immunological privilege, which may facilitate clinical interventions such as gene therapy and RPE transplantation.

[Tamoxifen retinopathy: a case series of clinical and functional data]. / Tamoxifen-Retinopathie: Eine Fallserie von klinischen und funktionelle Daten.

BACKGROUND: Tamoxifen is used in the treatment of selected patients with breast carcinoma. Rarely, it has been shown to cause ocular toxic effects including crystalline retinopathy. METHODS: Retrospective analysis of clinical and functional (visual acuity, visual field, colour vision) data of a case series of eight female patients under tamoxifen therapy with electrophysiological examination. RESULTS: Seven of eight patients complained of visual disturbances. In one case, examination showed crystalline deposits in the cornea and macular area. Three patients revealed changes in full-field and multifocal electroretinogram, and two had a pathological multifocal electroretinogram only. In six cases we applied a desaturated panel D-15 colour vision test; five of these showed some disorders. CONCLUSIONS: Most tamoxifen patients who complained of visual disturbances showed electrophysiological changes, particularly in the multifocal electroretinogram and often without a certain morphological correlate. We recommend electrophysiological examination for patients with unclear visual deterioration who are receiving tamoxifen therapy.

[Clinical diagnostic prerequisites for adult vitelliform macular dystrophy]. / Adäquate klinische Diagnostik der adulten vitelliformen Makuladystrophie.

BACKGROUND: Adult vitelliform macular dystrophy (AVMD) was first described in 1974 (Gass) but is still often misdiagnosed. Large studies using modern morphological and functional diagnostic methods do not exist. PATIENTS AND METHODS: The records of 67 consecutive AVMD patients (1994-2003) were reviewed regarding color vision, perimetry, RPE autofluorescence, fluorescein angiography, EOG, ERG, and mfERG. RESULTS: The mean age was 54.8 years. Symptoms, visual loss, color vision deficits, and visual field defects were highly variable. Autofluorescence was increased centrally in 77% of the eyes. In the ERG, the 30 Hz flicker response was reduced in 71% of the eyes. MfERGs showed a marked central amplitude reduction in 62% of the eyes and a continual normalization of the P1 amplitude towards the periphery. CONCLUSION: The enhanced autofluorescence indicates increased lipofuscin in the vitelliform lesions. The electroretinographic recordings reveal a moderate generalized cone dysfunction with increased severity towards the fovea. Ophthalmoscopy, autofluorescence, and recording of mfERG are prerequisites to diagnose AVMD correctly.

[Hereditary retinochoroidal dystrophies. Part 2: differential diagnosis]. / Hereditäre Netzhaut-Aderhaut-DystrophienTeil 2: Differenzialdiagnose.

A generally accepted classification for inherited retinochoroidal dystrophies does not exist. The names given to certain disorders are either based on ophthalmoscopic findings, or on histologic, electrophysiologic and genetic findings. Future research on the molecular genetic background will result in better definition of clinical entities. The purpose of this project is to outline a practical approach to inherited retinochoroidal dystrophies. For this reason, disorders with similar clinical symptoms are grouped together. Generalized retinochoroidal dystrophies affecting all retinal areas can be distinguished from regional dystrophies. Generalized dystrophies can be subdivided into those with peripheral onset, usually associated with initial rod function loss (night blindness, peripheral field loss: e.g. retinitis pigmentosa, choroideremia) and those with central onset associated with cone function loss (visual acuity loss, central scotoma, color vision deficits: e.g. cone or cone-rod dystrophies). Regionally limited dystrophies include the multitude of macular dystrophies and the autosomal dominant vitreoretinochoroidopathy, which remains limited to the periphery. It is important for a differential diagnosis to exclude involvement of other organ systems in syndromic disorders. Stationary inherited retinal dysfunction (e.g. monochromatism, congenital stationary night blindness) and other inherited or acquired diseases have to be excluded as well. Guidelines for differential diagnosis are presented.

[Hereditary retinochoroidal dystrophies. Part 1: Pathogenesis, diagnosis, therapy and patient counselling]. / Hereditäre Netzhaut-Aderhaut-DystrophienTeil 1: Pathogenese, Diagnostik, Therapie, Patientenbetreuung.

Hereditary retinochoroidal dystrophies are a heterogeneous group of disorders characterised by progressive loss of visual acuity or visual field. They can manifest at every age of life. The basic knowledge of retinal physiology and pathophysiology, diagnostic approach, therapeutic limitations and patient counselling are summarised. Hereditary retinochoroidal dystrophies are usually monogenic disorders. The diagnosis is based on a combined assessment of patient history and the results of morphological, electrophysiological, psychophysical and molecular genetic evaluations. Patients should undergo measurement of refraction and visual acuity testing, perimetry, ophthalmoscopy, full-field and multifocal electroretinography. Additional methods, e.g. fluorescein angiography, electrooculography or laboratory testing are helpful in certain cases. For promising new methods like measurement of retinal pigment epithelium autofluorescence or optic coherence tomography further evaluation of their value for differential diagnosis is required. General molecular genetic testing is still limited due to technical and financial limitations. A detailed differential diagnosis and long-term follow-up are advisable for patient counselling and the development of new therapeutic options. To date, therapy is limited. Major tasks for the ophthalmologists are providing low vision aids and adequate patient counselling.