Severe bilateral panuveitis in a patient with asymptomatic Epstein-Barr virus infection.
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Acute Disease↗
Biomedical subjects
D Pauleikhoff
Publications and source records attributed to D Pauleikhoff.
EFEMP1 is not associated with sporadic early onset drusen.
The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude that EFEMP1 is unlikely to be involved in the disease in this patient group. This suggests that mutations in a different as yet unknown gene or genes may lead to the early onset drusen phenotype.
Adult↗
Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration.
BACKGROUND: A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified. METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology. CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.
Adult↗
[Volume determination of pigment epithelium detachment in AMD by laser scanning tomography].
BACKGROUND: The possibility of using 3D mapping of AMD-related RPE detachments by means of laser scanning tomography was evaluated to correlate the fluorescein and tomographic findings. METHODS: Sixty eyes with AMD-related RPE detachments of 55 consecutive patients (19 men, 36 women) between 54 and 87 years of age (mean: 72.2 years) were examined using the Heidelberg Retina Tomograph (HRT). The parameters considered were area, volume, maximal height and 3D configuration of the RPE detachments. The tomographic data were analyzed and correlated with the fluorescein angiographic findings. Follow-up examinations were done at 3 and 6 months later. RESULTS: The mean +/- SD area of elevation was 10.59 +/- 5.51 mm2 (range, 0.93-19.73), which correlated well with the angiographic measurements. The mean maximal height was 0.42 +/- 0.19 mm (range, 0.11-0.83), mean volume was 2.55 +/- 1.9 mm3 (range, 0.073-6.63). We found a tendency to grow for untreated RPE detachments, depending on the volume at the first measurement. Three RPE detachments of high volume (mean 0.501 +/- 1.3 mm3) resulted in tearing of the RPE. The angiographic findings of localized neovascularizations in the RPE detachment area (39 of 60 eyes) showed a corresponding irregularity of the surface in most of the correlating 3D HRT figures. CONCLUSIONS: Confocal laser scanning tomography allows analysis of 3D configurations and a quantitative measurement of RPE detachments in AMD. Therefore, this diagnostic technique appears to be useful, especially for differentiated follow-up examinations (as in therapy-control studies). Furthermore, the analysis of 3D configurations seems to be useful to estimate the risk of tearing of the RPE and may help to indicate underlying neovascularizations.
Aged↗
[Adhesive properties of basal membranes of Bruch's membrane. Immunohistochemical studies of age-dependent changes in adhesive molecules and lipid deposits].
BACKGROUND: In addition to deposition of debris between the plasma and basal membrane of the RPE, different types of early and late AMD-like drusen, choroidal neovascularization and pigment epithelial detachments are characterized by splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer. Because these layers are normally attached by adhesion molecules, the possible age-related regression of these adhesion molecules in this structure was examined. METHODS: The presence of the adhesion molecules laminin, fibronectin, collagen IV and of lipid deposits was examined in 44 macular specimen (age 4-88 years). RESULTS: Age-related regression of the adhesion molecules laminin, fibronectin and collagen IV was observed in the basement membrane of the RPE and the endothelium cells of the choriocapillaris. This effect correlated with an increase in lipid deposits. CONCLUSION: The regression of adhesion molecules, especially in the basement membrane of the RPE in association with increased lipid deposits in Bruch's membrane, may explain the development of a "cleavage edge" for the splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer.
Adolescent↗
Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration.
Recently, the VMD2 gene has been identified as the causative gene in juvenile-onset vitelliform macular dystrophy (Best disease), a central retinopathy primarily characterised by an impaired function of the retinal pigment epithelium. In this study we have further characterised the spectrum of VMD2 mutations in a series of 41 unrelated Best disease patients. Furthermore we expanded our analysis to include 32 unrelated patients with adult vitelliform macular dystrophy (AVMD) and 200 patients with age-related macular degeneration (AMD). Both AVMD and AMD share some phenotypic features with Best disease such as abnormal subretinal accumulation of lipofuscin material, progressive geographic atrophy and choroidal neovascularisation, and may be the consequence of a common pathogenic mechanism. In total, we have identified 23 distinct disease-associated mutations in Best disease and four different mutations in AVMD. Two of the mutations found in the AVMD patients were also seen in Best disease suggesting a considerable overlap in the aetiology of these two disorders. There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD.
Adolescent↗
A fluorescein and indocyanine green angiographic study of choriocapillaris in age-related macular disease.
OBJECTIVE: To examine the phenomenon of a prolonged choroidal filling phase (PCFP) as seen on fluorescein and indocyanine green (ICG) angiography in patients with early age-related macular disease (AMD). METHODS: One hundred eyes of consecutive patients with early AMD were studied. Patchy and slow choroidal filling in early fluorescein and distinct areas of reduced choroidal fluorescence in ICG angiography were interpreted as PCFP. In addition, associated drusen characteristics and the AMD status of the fellow eye were recorded. RESULTS: A PCFP was observed in 26% of eyes using fluorescein and 32% of eyes using ICG angiography, with good concordance between findings using both techniques (K = 0.9). A PCFP was associated with confluent drusen (P = .01), the presence of focal retinal pigment epithelial-atrophic patches in the study eye (P=.005), and geographic atrophy in the fellow eye (P=.03). Other drusen characteristics and the distribution of visual acuity (P = .90) were not different between eyes with and without PCFP. CONCLUSIONS: A PCFP on fluorescein and ICG angiography is a common feature in early AMD. This sign has been interpreted as indicating reduced choroidal perfusion caused by change in diffusional characteristics of Bruch membrane. A PCFP is a clinical marker for diffuse deposits in Bruch membrane and a risk factor for the development of geographic atrophy.
Aged↗
[Autofluorescence characteristics of lipofuscin components in different forms of late senile macular degeneration].
BACKGROUND: Lipofuscin is the main fluorophore of the human fundus. Because lipofuscin is the result of the accumulation of metabolic debris in pigmentepithelial cells (RPE), the autofluorescence can be interpreted as a clinical sign for the metabolic activity of the RPE. In order to get informations of RPE-function in different types of late AMD, the autofluorescence patterns in patients with late AMD were analyzed. MATERIAL AND METHOD: A prospective examination of the fundus-autofluorescence of 64 eyes of 52 patients with different types of late AMD was performed using a confocal scanning-laser-opthalmoscope. The autofluorescence images were categorized in respect to the type of late AMD according to the opthalmoscopic and fluoresceine-angiographic findings. RESULTS: Reduced autofluorescence was found in the centre of occult (78.6%) and classic (100%) choroidal neovascularisations (NV) as well as in the occult NV of RPE detachments. A loss of autofluorescence was related to the RPE free area of RPE-tears (100%) and to RPE-atrophy (88.9%) with sometimes increased autofluorescence at the rim. Increased autofluorescence could be seen at the surface of RPE-detachments (71.4%), in the area of the shrink age of RPE in RPE-tears (100%) as well as at RPE-proliferations in small occult NV (100%). Disciforme scars showed variable patterns of autofluorescence. CONCLUSION: The autofluorescence of the RPE can be analyzed clinically with the described method. Different patterns of autofluorescence could be revealed in different types of late AMD. Increased autofluorescence was found in lesions with proliferative or phagocytotic metabolic activity of the RPE like RPE-detachments, shrinked RPE in RPE-tears or occult NV with RPE-proliferations. The reduced autofluorescence in occult or classical choroidal NV can be interpreted as a sign of decompensation of the RPE and was also seen in areas with RPE-loss.
Aged↗
[Focal proliferations of retinal pigment epithelium. Risk factor in senile macular degeneration].
BACKGROUND: Clinical studies have demonstrated the relevance of focal RPE proliferations in early AMD as risk factors for visual loss caused by late AMD. Angiographically these focal RPE proliferations are characterized as small hypofluorescent spots with hyperfluorescent rim without leakage. Corresponding to histological and experimental studies they can be interpreted as small areas of occult choroidal neovascularizations covered by proliferated RPE cells. The characterization of the long-term prognosis of these lesions was the aim of the present study. PATIENTS AND METHODS: Ninety-eight patients (52 female, 46 male) were reexamined clinically and angiographically with a follow-up of 2-12 years (mean 6.5 years). RESULTS: Visual loss of two lines or more could be observed in 64.5% of patients with final visual acuity less than 20/100 in 24.5% of patients. Morphologically the changes in visual acuity were related to the progression towards classical choroidal neovascularizations in 32.7% of patients. In addition 11.2% of patients demonstrated a regression of the small occult membrane with the development of small areas of RPE atrophy covering the size of the original occult neovascularization. In 10.2% of the patients enlargement of the lesion was observed, resulting in a large occult choroidal neovascularization without signs of classical membranes, and in 45.9% of patients the clinical and angiographical situation was unchanged. The most important prognostic factor correlating with visual loss was the presence of a disciform lesion in the fellow eye and of multiple drusen in the examined eye. Other factors like the size or location of the focal RPE proliferation and the duration of follow-up did not correspond with visual loss. CONCLUSIONS: Focal RPE proliferations in early AMD interpreted as small occult choroidal neovascularizations are associated with a high risk of visual loss. Especially if these lesions are associated with multiple drusen and a disciform lesion in the fellow eye, nearly all patients are at risk for visual loss. These changes may therefore characterize a special high-risk group for future prophylactic treatments in early AMD, but because of the high risk for the development of classical choroidal neovascularizations in this group, these results are also very important for the planning of prophylactic laser trials for drusen in early AMD.
Aged↗
Clinical and genetic evidence for autosomal dominant North Carolina macular dystrophy in a German family.
PURPOSE: To describe a German family with clinical and genetic evidence of autosomal dominant North Carolina macular dystrophy. METHODS: Twenty-six individuals from a five-generation family from northern Germany were investigated clinically. In addition, we performed genetic linkage analyses using polymorphic markers from proximal 6q. RESULTS: The affected family members showed clinical abnormalities consistent with North Carolina macular dystrophy including multiple drusen, choroidal neovascularization in one patient, and geographic atrophy in elderly patients. The DNA analyses demonstrated significant linkage to the North Carolina macular dystrophy locus on chromosome 6q14-q16.2. CONCLUSION: Our findings provide strong evidence of a German pedigree with an autosomal dominant macular dystrophy manifesting with clinical abnormalities consistent with North Carolina macular dystrophy.
Adolescent↗
[Cryocoagulation in therapy of proliferative diabetic retinopathy].
BACKGROUND: The importance and indication of panretinal photocoagulation in proliferative diabetic retinopathy is well established. In contrast the indication of cryotherapy in this disease is more controversial especially in regard of new indications for early vitrectomy. The present study was performed to characterize the clinical possibilities and limitations of cryotherapy in complicated proliferative diabetic retinopathy. PATIENTS AND METHODS: In 231 patients with proliferative diabetic retinopathy and vitreous hemorrhage limiting further photocoagulation the visual outcome and diabetic retinal changes were observed before and after cyrotherapy (15-20 effects) of the ophthalmoscopically visible peripheral retina. RESULTS: After cryotherapy regression of active proliferations could be seen in 70% of the patients. Resorption of vitreous hemorrhages could be found in 80% of the patients. This was associated with improvement in visual acuity in 50-60% of the patients. Loss of vision was caused due to tractional detachment in 20% of the patients and due to further vitreous hemorrhages in 10% of the patients. Comparison of retinal changes between patients with worsened visual acuity and patients with increase in visual acuity demonstrated the preoperative fibrotic status of disc neovascularisation as the most important prognostic factor. The development of central tractional detachment was significantly higher in patients with preoperatively partly regressed disc neovascularisation. CONCLUSIONS: Cryotherapy of the peripheral retina in proliferative diabetic retinopathy with vitreous hemorrhages is therefore only indicated after ophthalmoscopical or echographical exclusion of peripapillary fibrosis and retinal traction and with sufficient visibility of the peripheral retina for the application.
Adult↗
An ancestral core haplotype defines the critical region harbouring the North Carolina macular dystrophy gene (MCDR1).
Autosomal dominant North Carolina macular dystrophy (NCMD) or central areolar pigment epithelial dystrophy (CAPED) is an allelic disorder that maps to an approximately 7.2 cM interval between DNA markers at D6S424 and D6S1671 on 6q14-q16.2. The further refinement of the disease locus has been hindered by the lack of additional recombination events involving the critical region. In this study, we have identified three multigeneration families of German descent who express the NCMD phenotype. Genotyping was carried out with a series of markers spanning approximately 53 cM around the NCMD locus, MCDR1. Genetic linkage between the markers and the disease phenotype in each of the families could be shown. Disease associated haplotypes were constructed and provide evidence for an ancestral founder for the German NCMD families. This haplotype analysis suggests that a 4.0 cM interval flanked by markers at D6S249 and D6S475 harbours the gene causing NCMD, facilitating further positional cloning approaches.
Chromosomes, Human, Pair 6↗
[Fluorescence angiography in age-related macular degeneration. Study of the incidence of lesions treatable with coagulation].
BACKGROUND: The treatment of late age-related Macular Degeneration (AMD) according to the results of prospective clinical studies is indicated in classical choroidal neovascularisations (NV), which can be delineated from the center of the fovea. To evaluate the effectiveness of this therapy, the knowledge of the frequency of treatable lesions in the spectrum of late AMD is important. PATIENTS AND METHODS: The frequency of different manifestations of late AMD and of lesions treatable with photocoagulation according to the results of prospective clinical studies was recorded in a consecutive series of 2503 fluorescein angiogramms in patients with symptomatic late AMD. RESULTS: Classical choroidal NV could be detected in 35.4% of the patients. In 5.5% of the patients these NV were extra- or juxtafoveolar and therefore laser treatment could be recommended. 10.2% of the patients demonstrated small (< 1 PD) subfoveal classical NV and 20.4% of the patients showed large (> 1 PD) subfoveal NV or membranes associated with large subfoveal, subretinal hemorrhages. Occult choroidal NV could be seen in 41.8% of the patients. These occult NV were larger 1 PD in 21.9% of the patients and small (< 1 PD) in 19.9% of the patients. Pigment epithial detachments (PED) could be seen in 14.6% of the patients (9.9 vascular PED, 3.7% avascular PED, 1.0% rip of the retinal pigment epithelium). Disciform scars were present in 7.2% of the angiogramms. CONCLUSIONS: The spectrum of late AMD can be differentiated in several clinical features. In this consecutive series of 2503 symptomatic AMD patients only appr. 6%% of the patients could be treated with laser treatment according to the results of prospective clinical studies. Because in addition the success of this treatment is very limited, the development of new therapeutic options is one of the major tasks in ophthalmology.
Aged↗
[Late vision loss after focal hemorrhagic chorioretinopathy].
Prospective clinical studies about photocoagulation of extrafoveolar choroidal neovascularizations in focal hemorrhagic chorioretinopathy (CR) have demonstrated that the risk of visual loss years after successful treatment is related to the development of retinal pigment epithelium (RPE) atrophy around the laser scar. The reason for this event was thought to be late damage of RPE cells due to the laser treatment. However, because RPE atrophy can also be seen in untreated patients, a prospective study was started to test this pathogenetic hypothesis and to analyze the pathogenetic factors and prognostic importance of RPE atrophy in focal hemorrhagic CR. Eighty-eight patients (52 women, 36 men, 15-45 years old; mean follow-up 62 months; 26 patients treated by photocoagulation) with focal hemorrhagic CR were reexamined. Fifty-two patients (15 treated by photocoagulation and 37 untreated) showed clinically visible RPE atrophy. In these 52 patients the initial and final visual acuity, the amount of initial subretinal fluid (34.6% < 500 microns, 50% 500-750 microns, 15.4% > 750 microns) and the amount RPE atrophy (23.2% < 500 microns, 53.6% 500-750 microns, 23.2% > 750 microns) were analyzed. The development of RPE atrophy was dependent on the time of follow-up (36 patients without RPE atrophy, mean follow-up 29 months; 52 patients with RPE atrophy, mean 84 months, P < 0.001). Of the 52 patients with RPE atrophy, 15 were treated by photocoagulation. The distribution of RPE atrophy was similar to what was found in the 37 untreated patients (P = 0.4). With pronounced RPE atrophy, a decrease in final visual acuity was seen (RPE atrophy < 500 microns, mean visual acuity 0.5; 500-750 microns mean visual acuity 0.3; > 750 microns, mean visual acuity 0.1; P = 0.005). Increased RPE atrophy was also associated with a higher incidence of visual loss (p = 0.009). The amount of RPE atrophy was not dependent on the time of follow-up (P = 0.3), but only correlated with the initial amount of subretinal fluid (atrophy < 500 microns: subretinal fluid < 500 microns 15.4%, 500-750 microns 7.7%, > 750 microns 0%; atrophy 500-750 microns: subretinal fluid < 500 microns 19.2%, 500-750 microns 32.7%, < 750 microns 1.9%; atrophy > 750 microns: subretinal fluid < 500 microns 0%, 500-750 microns 9.6%, > 750 microns 13.5%; P < 0.0001). Because RPE atrophy in focal hemorrhagic CR was seen in patients both with and without photocoagulation therapy, laser treatment cannot be the causative factor. With increased follow-up the risk of the development of RPE atrophy increases in all patients. The resulting amount of RPE atrophy was only dependent on the initial amount of subretinal fluid. If the fovea is included in the exudative detachment, there is a higher risk of long-term visual loss.
Adolescent↗
[Age-related macular degeneration. 1. Epidemiology, pathogenesis and differential diagnosis].
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Adolescent↗
[Age-related macular degeneration. 2. Therapeutic approaches].
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Aged↗
Prevalence of age-related macular degeneration.
Early and late age-related macular degeneration (AMD) have a high prevalence in elderly patients but may be differentiated by medical or environmental factors, eg, hypertension, geographic area, or antioxidant agents. Because nuclear sclerotic cataract is associated with AMD both aging changes may share a common pathogenesis. The genetic predisposition for AMD is indicated by the identical appearance in monozygotic twins, but genetics may be also important for the explanation of the low incidence of late AMD in black individuals. Specific ocular characteristics like light or depigmented iris color, prolonged dark adaptation, and decreased foveal flicker sensitivity are also risk factors for AMD. Early AMD characteristics with high risk for late AMD are confluent drusen, focal hyperpigmentation, or atrophy and slow choroidal fluorescein filling. Therefore specific genetic, environmental, medical, and ocular characteristics determine the individual appearance and progress of AMD. The knowledge of these factors may result in new prophylactic and specific treatments for AMD.
Aged↗
Analysis of lipid deposits extracted from human macular and peripheral Bruch's membrane.
OBJECTIVE: Lipids in Bruch's membrane may affect the evolution of age-related macular disease. To determine whether these show differences in regional distribution, we analyzed lipid deposits in Bruch's membrane at macular and peripheral sites. METHODS: Thin-layer chromatography was used to measure different lipid classes extracted from macular and peripheral Bruch's membrane of 32 eye bank eyes. RESULTS: The quantity of lipid extracted was consistently higher in the macula than in the periphery of human eyes. The total from both sites and the difference between the sites increased with age. The extracted lipids consisted largely of phospholipids, triglycerides, fatty acids, and free cholesterol. There was little cholesterol ester. CONCLUSIONS: Accumulation of lipids with age appears to be greater in the central than in the peripheral region of the fundus, indicating that lesions in age-related macular degeneration and Bruch's membrane lipid deposits share a common spatial distribution. The composition is consistent with the lipids being of cellular origin.
Adolescent↗