[Genetic studies of age related macular degeneration]. / Genetische Untersuchungen bei altersabhängiger Makuladegeneration.

While during the 1980s epidemiological studies searched for possible associations of environmental factors, factors of lifestyle, and cardiovascular diseases with age-related macular degeneration (ARMD), this is now perceived as a multifactorial disorder with predisposing genetic constellations and with environmental factors contributing to disease progression. The evidence which supports a genetic background of ARMD comes from population-based studies as well as from familial aggregation and twin studies. Meanwhile, the knowledge about the genetics of ARMD has increased, however, the search for the genetic basis faces challenges and due to the late onset there is usually only one generation available for studies. Moreover, uncertainty surrounds the diagnosis in previous generations but nonetheless, ARMD is clinically heterogeneous and some ambiguity exists concerning the earliest signs. In this article, the current state of genetic research into ARMD as well as the techniques to approach this complex disorder will be discussed.

[Early clinical results with mycophenolate mofetil in immunosuppressive therapy of ocular pemphigoid]. / Erste klinische Erfahrungen mit Mycophenolatmofetil bei der immunsuppressiven Therapie des okulären Pemphigoids.

BACKGROUND: Ocular cicatrical pemphigoid can lead to severe structural damage or loss of vision at worst. Longterm therapy with dapsone or systemic immunosuppressive therapy, e.g. with cyclophosphamide is often inevitable. Immunosuppression may cause severe side effects in some patients. PATIENTS AND METHODS: Data are presented on 5 patients with ocular cicatrical pemphigoid who were treated with mycophenolate mofetil 2 g daily. Criterion of effectiveness was the clinical course of the condition defined as nonprogression of the morphologic alterations. Patients were initially examined and interviewed routinely every four weeks for the first four months, then every eight weeks. Patients were asked about side effects and underwent monthly blood checks. RESULTS: All patients were followed for at least 12 months. Mycophenolate mofetil proved to be effective with respect to the clinical course in 9 out of 10 eyes. All patients showed regression of inflammatory conjunctival alteration and improvement of their complaints. In one eye the inflammatory process restarted after surgery due to excessive symblephara had been performed. Gastrointestinal side effects were reported in the initial phase, e.g. lack of appetite, nausea and mild diarrhoea. CONCLUSIONS: Mycophenolate mofetil proved to be an effective immunosuppressant for the treatment of ocular cicatrical pemphigoid. Namely side effects were less severe and frequent compared to those known from other currently administered immunosuppressants. Longterm results and larger case numbers are needed to sustain these early results.

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.