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Pseudoexfoliation syndrome (PEX) is a systemic disorder characterized by the deposition of an abnormal fibrillar material in ocular and various extraocular tissues. It represents the most common identifiable cause of glaucoma (PEX glaucoma = PEXG). Due to similar pathogenetic mechanisms, glaucoma has been called "ocular Alzheimer's disease". PEXG and Alzheimer's disease share common associations such as the higher prevalence of hyperhomocysteinemia in both disorders. In order to investigate the cause of hyperhomocysteinemia in PEXG, we evaluated B-vitamin levels (folate, B12, B6) and their associations with homocysteine (Hcy) in plasma of 70 PEXG patients and 70 control subjects. Folate, vitamin B12 and B6 levels were significantly decreased and associated with elevated Hcy levels in PEXG. Low B-vitamin levels in PEX might also help explain, at least in part, the higher prevalence of B-vitamin deficiency in disorders associated with PEX such as Alzhemier's disease.

Introduction: Corpora amylacea (CAm) occur in the optic nerve and in retinal ageing and degeneration. Cellular expression of L-kynurenine aminotransferases (KAT I and II) in the avian and rodent retina and its changes in retinal development and neurodegeneration have been documented. This study examines KAT I and II immunoreactivity in CAm in the human retina and optic nerve., Material and Methods: Immunohistochemistry was performed using polyclonal antibodies against KAT I and KAT II on sections of 23 human eyes enucleated for malignant uveal melanoma. Occurrence and location of KAT I- or KAT II-stained CAm was compared with PAS-stained sections., Results: KAT I and KAT II expression in CAm has been shown in the retina and optic nerve with similar location to PAS-stained sections. KAT I immunoreactivity was more intense than KAT II and its staining was more pronounced in the retrolaminar part of the optic nerve. Some of the CAm showed only faint KAT II expression and occasionally there was no staining. KAT II revealed no association of staining variability and localisation of CAm. Similarly to animal studies, in the human retina KAT I was observed on Müller cell endfeet while KAT II was expressed in retinal ganglion cells., Conclusions: Presence of kynurenine aminotransferases in CAm in the human retina and optic nerve suggest that both enzymes may be involved in mechanisms of retinal ageing and neurodegeneration leading to CAm formation.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

Background: Flicker light is an easy method to test sensory function after stress. The aim of this study was to determine the influence of flicker stress on temporal contrast sensitivity in healthy controls and patients with glaucomatous alteration of the optic disk., Methods: A commercially available full-field stimulator (Retiport, Roland Consult) equipped with white LEDs was modified to perform psychophysical tests. The patients underwent measurements of the recovery time interval from cessation of flicker stress until recognition of a pregiven flicker contrast after photo stress. In addition, we studied contrast sensitivity with a continuous flickering target and with a flicker burst protocol avoiding adaptation to prevailing flicker. All tests were performed at a constant retinal illumination and at a frequency of 37 Hz for provocation as well as for contrast sensitivity tests., Subjects: Normal healthy controls (40), "preperimetric" (62), and "perimetric" (52) open-angle glaucoma patients were studied. Exclusion criteria were age lower than 31 years, visual acuity under 0.6, and perimetric mean defect more than 9.5 dB., Results: Recovery time after flicker stress was significantly longer in patients than in normals and longer in perimetric than in preperimetric patients. Analysis in perimetric patients revealed a larger area under ROC for the provocation test (0.95) than in contrast sensitivity tests (continuous flicker method: 0.90, flicker burst mode: 0.84)., Conclusion: High-power LEDs which are installed in modern full-field devices can be used as a helpful tool to study psychophysical properties. In the present study it could be shown that threshold, adaptation, and recovery of temporal transfer characteristics are impaired in many patients with glaucoma.

Purpose: The aim of this study was to determine, whether the combination of morphologic data of the optic nerve head and visual field (VF) data would improve diagnosis of glaucoma, on the basis of the measurements alone., Patients and Methods: Eighty-eight perimetric glaucomatous and 88 normal optic discs from the Erlangen Glaucoma Registry were matched for age. All normals and patients were examined in a standardized manner (Slitlamp biomicroscopy, gonioscopy, 24 h-applanation tonometry, automated VF testing, 15-degree optic disc stereographs, and Heidelberg Retina Tomograph (HRT)-scanning of the optic disc). The HRT variables were calculated in 4 optic disc sectors. All variables were calculated with the software's standard reference plane. To gain the same allocation of sectors as provided by the HRT software, the VF responses were averaged within 4 sectors. Classification results of these VF responses were compared with the summarized results within 4 sectors. Six different combinations of morphologic and VF data were used to assess their suitability to diagnose the disease. HRT measurements, and the standard output of the Octopus (HRT/PERI1), HRT measurements and the summarized sectors and their standard deviations (HRT/PERI2), HRT measurements, standard output of the octopus and the summarized sectors and their standard deviations (HRT/PERI1/PERI2), standard output of the Octopus (PERI1), summarized sectors of the Octopus and their standard deviations (PERI2) and HRT measurements. To assess the diagnostic value of the different data sets machine learning classifiers, stabilized linear discriminant analysis, classification trees, bagging, and double-bagging were applied., Results: Combination of morphologic and VF data improved the automated classification rules. The accuracy to diagnose glaucoma just by VF and HRT indices was maximized for double-bagging using both diagnostic tools. An estimated misclassification probability of less than 0.07 could be achieved for the primary open angle glaucoma patients combining HRT and VF sectors by double bagging. So highest sensitivity was 95% and specificity 91%, achieved by double-bagging and combination of HRT, PERI1, and PERI2., Conclusions: The combination of optic disc measurements and VF data could not only improve glaucoma diagnosis in future, but could also help to find an objective way to diagnose glaucomatous optic atrophy. The limitation of the topographic relationship between structure and function is the individual variability of the optic disc morphology and the subjective variability of VF testing.

Purpose: To determine the role of the extracellular chaperone clusterin in the pathophysiology of pseudoexfoliation (PEX) syndrome/glaucoma, which is characterized by the stable deposition of abnormal extracellular fibrillar material in anterior segment tissues., Methods: Real-time PCR, in situ hybridization, and immunohistochemistry were applied to analyze the mRNA and protein expression of clusterin in PEX eyes of patients without and with glaucoma and to compare them with eyes of patients with primary open-angle glaucoma and angle-closure glaucoma and with normal control eyes. Aqueous levels of clusterin were determined by Western blot analysis. Real-time PCR and Western blot analysis were used to study the effect of TGF-beta1, which is significantly increased in the aqueous humor of PEX eyes, on clusterin expression by nonpigmented ciliary epithelial cells in vitro., Results: Clusterin mRNA was ubiquitously expressed in most ocular cells and tissues, particularly in the epithelium of ciliary processes, whereas the protein was mostly located to extracellular structures, such as ocular basement membranes and stromal fibers. Real-time PCR and in situ hybridization displayed significant downregulation of clusterin mRNA in all anterior segment tissues of PEX eyes, irrespective of the presence or type of glaucoma, compared with normal and glaucomatous control eyes, whereas posterior segment tissues did not show any differential expression. A generally decreased immunoreactivity, but a prominent binding of clusterin to all PEX deposits, could be observed in ocular tissues of PEX eyes. Clusterin levels in aqueous humor were significantly reduced in eyes of patients with PEX syndrome compared with normal and glaucomatous control eyes. The expression of clusterin mRNA and protein in nonpigmented ciliary epithelial cells was significantly downregulated by TGF-beta1 in vitro., Conclusions: Considering the known role of clusterin as a highly efficient extracellular chaperone, its deficiency in the anterior segment of PEX eyes may promote the stress-induced aggregation and stable deposition of the pathologic extracellular matrix product characteristic of PEX syndrome.

Background: Vascular dysregulation in open-angle glaucomas can be identified by measuring the blood circulation during exposure to cold water. Aim of this study was to find out whether the same cold stimulus would lead to functional changes in the visual evoked potentials (VEP) of the short-sensitive pathway in normals and glaucoma patients., Patients and Methods: Blue-on-yellow pattern-visual evoked potentials were studied in 22 healthy control persons and 47 patients with primary open-angle glaucoma (25 high-pressure glaucomas, 22 normal pressure glaucomas with clinical signs of vasospastic hyperreactivity). A blue stripe pattern, presented in onset-offset mode on a yellow adaptation light served as the stimulus. Cold provocation was initiated by dipping one hand of the patient into cold water of 3 degrees C to 5 degrees C. The onset amplitudes and peak times were measured without cold exposition as well as two and four minutes after the cold exposition began., Results: In the group of vasospastic glaucoma patients a significant reduction of visual evoked potential-amplitudes was observed during cold provocation (amplitude before ice exposition: 4.17 microV, amplitude following two minutes of ice exposition: 3.52 microV; paired test: P < 0.01). Other subject groups showed no significant amplitude reductions after cold provocation. Peak times of both open-angle glaucoma groups (132.3 +/- 18.7 milliseconds in high pressure, 132.7 +/- 14.5 milliseconds in normal pressure) were significantly increased in comparison to normals (117.4 +/- 8.0 milliseconds). However, no significant influence of the cold provocation on peak times could be found in all groups., Conclusion: Peak times of the blue-on-yellow visual evoked potentials are significantly prolonged in patients with primary open-angle glaucomas. Cold provocation causes a significant amplitude reduction of the blue-on-yellow visual evoked potential in the present normal-pressure glaucoma patients and reflects vascular dysregulation in patients with vasospastic hyperreactivity.

Purpose: To perform a correlation between morphology and function by studying local perimetric field losses and thickness reduction of the nerve layer in corresponding areas., Method: Forty-seven patients with "preperimetric" open-angle glaucoma, 95 patients with "perimetric" open-angle glaucoma, and 75 control subjects had perimetric (Octopus) and polarimetric measurements. Criteria for exclusion: optic discs larger than 4 mm, media opacities, polarimetric hourglass pattern in the macular image. Thickness values of the retinal nerve fiber layer were determined in 14 upper and 14 lower sectors (10 degrees each) as well as nasally and temporally (40 degrees each) as provided from the GDx (software version 4000). The healthy control subjects served to determine age-corrected thickness deviation in all sectors. Analyses were calculated in eight nerve fiber bundle related areas. Due to non-linear relationships between perimetric defects and corresponding thickness deviation non-parametric tests were used., Results: Localized visual field defects in the present perimetric patients were highest in upper and lower visual field areas abutting the nasal meridian. Thickness loss of nerve fiber layer however was highest in more circumferential upper and lower nerve fiber bundles. Correlations between local mean defects and deviation of the retinal nerve fiber layer thickness from normals showed a clear association for corresponding areas. The correlation coefficients were significant (P < 0.01) for all arcuate superior and inferior visual field zones except horizontally and not for the area of the lower nasal step., Conclusion: The present correspondence map indicates that focal perimetric defects can be identified best polarimetrically if they occur in the arcuate bundles of the visual field. A lack of correspondence was observed in the area of the papillo-macular bundle.

Purpose: To estimate the prevalence of C677T single nucleotide polymorphism in the 5,10-methylentetrahydrofolate reductase (MTHFR) gene in primary open-angle glaucoma (POAG) and pseudoexfoliation open-angle glaucoma (PEXG)., Design: Case-control study, Methods: MTHFR was assessed in 147 patients (76 POAG, 71 PEXG) and 71 control subjects with cataract. Associations of genotypes were assessed by Armitage's trend test and the corresponding odds ratio (OR) for allele positivity with 95% confidence interval (CI)., Results: We observed significant evidence of a higher prevalence of C677T in POAG (9% homozygote, 49% heterozygote, 42% wildtype, P = .01, OR = 2.38, 95% CI 1.23-4.62), but not in PEXG (9% homozygote, 41% heterozygote, 50% wildtype, P = .09, OR = 1.78, 95% CI 0.91-3.50) compared with the controls (3% homozygote, 34% heterozygote, 63% wildtype)., Conclusions: The MTHFR C677T variant leading to moderate hyperhomocysteinemia may play a role in the pathogenesis of POAG acting as a genetic risk factor.

Purpose: To comparatively investigate the effects of TGF-beta(1) and TGF-beta(2) on extracellular matrix production, proliferation, migration, and collagen contraction of cultured human Tenon's capsule fibroblasts derived from patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma, primary open-angle glaucoma (POAG), and cataract., Methods: Tenon's capsule fibroblasts obtained from four groups of patients were cultured and stimulated with different concentrations (0.1-10 ng ml(-1)) of TGF-beta(1) or TGF-beta(2) for up to 14 days. Cell proliferation was determined with the WST-1 colorimetric assay, cell migration by using the Transwell assay system, and collagen contraction by computerised analysis of three-dimensional collagen lattices and immunohistochemistry for alpha-smooth muscle actin expression. Expression and synthesis of extracellular matrix components (fibronectin, collagen types I and III) was assessed by enzyme-linked immunosorbent assays, by real-time RT-PCR, and by transmission electron microscopy., Results: Both TGF-beta(1) and TGF-beta(2) in pathophysiological concentrations of 0.1-5 ng ml(-1) stimulated cell proliferation, migration, collagen contraction, alpha-smooth muscle actin expression as well as mRNA expression and secretion of fibronectin, collagen type I, and collagen type III by Tenon's fibroblasts derived from all groups of patients. TGF-beta stimulation occurred in a concentration-dependent manner with different peak activities associated with different fibroblast functions. There was some variability among the different groups of patients with an increased response of cells derived from PEX and POAG patients as compared to cataract patients. Although no statistically significant differences were found between both TGF-beta isoforms, TGF-beta(1) had a more pronounced stimulatory effect on expression and synthesis of extracellular matrix components including the production of elastic microfibrils, particularly in cells derived from patients with PEX syndrome/glaucoma., Conclusions: These findings suggest a significant contribution of TGF-beta(1) in addition to TGF-beta(2) to the conjunctival scarring process following glaucoma filtration surgery. Due to its pronounced fibrogenic potential, TGF-beta(1) may become another focus for targeting drug therapy, particularly in patients with PEX glaucoma.

Purpose: To determine total homocysteine levels in aqueous humor of pseudoexfoliation open-angle glaucoma patients., Design: Case-control study., Methods: Total homocysteine levels were measured by enzyme-linked immunosorbent assay in aqueous humor and plasma of 29 patients with pseudoexfoliation glaucoma and 31 control patients with cataract. Patients with factors affecting homocysteine levels were excluded., Results: We observed significantly elevated (twofold) homocysteine levels in the aqueous humor of the glaucoma patients (Z = -5.11, P <.0001). Additionally, the calculated ratio (plasma:aqueous humor) was significantly lower in these patients (Z = -3.57, P <.001), and aqueous homocysteine was significantly correlated with their respective elevated plasma levels (r =.42, P =.02)., Conclusions: Because homocysteine induces vascular injury and alterations of extracellular matrix, high aqueous homocysteine may trigger the abnormal matrix accumulation characteristic. It may reflect the proposed impairment of the blood-aqueous barrier of pseudoexfoliation open-angle glaucoma and be involved in its pathogenesis.

The authors investigated 17 patients with idiopathic intracranial hypertension (IIH), correlating laser scanning tomography of the optic nerve with CSF opening pressure. The decrease in papilla volume and papilla height showed a linear correlation with the opening pressure of the CSF (r = 0.59, p < 0.001; r = 0.63, p < 0.001). If the CSF opening pressure is higher than 20 cm water, an increase of 5 cm water CSF pressure corresponds to a papilla volume increase of 0.95 mm3 as well as a papilla height increase of 0.34 mm.

Purpose: In this article we propose and evaluate nonparametric tree classifiers that can handle non-normal data and a large number of possible predictors using the full set of standard Heidelberg Retina Tomograph measurements for classifying glaucoma., Methods: The classifiers were trained and tested using standard Heidelberg Retina Tomograph parameters from examinations of 98 subjects with glaucoma and 98 normal subjects of the Erlangen Glaucoma Registry. All patients and control subjects were evaluated by 15 degrees -optic disc stereographs, Heidelberg Retina Tomograph measurements, standard computerized white-in-white perimetry, and 24-hour-intraocular pressure profiles. The subjects were matched by age and sex. Standard classification trees as well as bagged classification trees were used. The classification outcome of the trees was compared with the classification by two published linear discriminant functions based on Heidelberg Retina Tomograph variables with respect to their cross-validated misclassification error., Results: The bagged classification tree had the lowest misclassification error estimate of 14.8% with a sensitivity of 81.6% at a specificity of 88.8%. The cross-validated error rates of the two linear discriminant function procedures were 20.4% (sensitivity 82.6%, specificity 76.7%) and 20.6% (sensitivity 81.4%, specificity 77.3%) for our set of observations. Bagged classification trees were able to reduce the misclassification error of glaucoma classification., Conclusions: Bagged classification trees promise to be a new and efficient approach for glaucoma classification using morphometric 2- and 3-dimensional data derived from the Heidelberg Retina Tomograph, taking into account all given variables.

Background: Macrodiscs with physiologic macrocups and elevated intraocular pressure (IOP) are frequently suspicious for glaucoma. Patients with an elevated c/d ratio and an IOP of more than 21 mmHg are often treated for glaucoma. We investigated a possible relationship between macrodiscs, IOP and central corneal thickness., Methods: Using the Erlangen glaucoma registry, 341 out of 1,096 consecutive patients with unremarkable and repeated visual field (Octopus 500, G1-3, MD<2.1) were selected. Most of these patients had been sent as glaucoma suspects. The following data were collected: corneal ultrasound pachymetry (Tomey, AL-2000), IOP profile, visual acuity and central corneal power. The morphometric analysis was performed by planimetry using the Littmann formula. Optic nerve heads with a disc area of more than 3.1 mm(2) were defined as macrodiscs., Results: Patients were subdivided into the following groups: group A: healthy macrodiscs, IOP <22 mmHg (87 patients); group B: healthy macrodiscs, IOP >21 mmHg (66 patients); group C: normal-sized healthy discs, IOP <22 mmHg (93 patients); group D: normal-sized healthy discs, IOP >21 mmHg (95 patients). Mean corneal thickness was: group A: 575+/-36 microm, group B: 596+/-37 microm, group C: 557+/-31 microm and group D: 585+/-38 microm ( P=0.003). Mean central corneal power measured: group A: 41.7+/-1.3 D, group B: 42.4+/-1.3 D, group C: 43.0+/-1.2 D and group D: 42.8+/-1.2 D ( P<0.05). The maximum of IOP was: group A: 17.6+/-3.1, group B: 26.2+/-4.1, group C: 17.2+/-3.4 and group D: 29.7+/-5.5 mmHg. Optic disc size measurements were: group A: 3.91+/-0.66, group B: 3.65+/-0.6, group C: 2.56+/-0.30 mm(2) and group D: 2.39+/-0.39 microm, respectively., Conclusions: Macrodiscs with elevated IOP have a higher corneal curvature (mean: +0.7 D) and a thicker central cornea (mean: +21 microm) compared to macrodiscs without elevated IOP. An exact evaluation of optic disc morphology in combination with pachymetric and keratometric measurements in relation to IOP could avoid an overtreatment in patients with suspect primary open-angle glaucoma.

Purpose: The aim of this study was to evaluate the diagnostic usefulness of the combined use of frequency-doubling technology (FDT) perimetry and polarimetry of the retinal nerve fiber layer., Design: Cross-sectional study., Methods: Seventy ocular hypertensive patients (normal optic disk and standard perimetry, elevated intraocular pressure [>21 mm Hg]), 59 patients with "preperimetric" open-angle glaucoma (glaucomatous optic disk atrophy, elevated intraocular pressure [>21 mm Hg], no visual field defect in standard perimetry), 105 patients with "perimetric" open-angle glaucoma (glaucomatous optic disk atrophy and clearly marked visual field defect), and 73 control subjects had FDT screening (protocol: C-20-5) and polarimetric measurements (GDx). Criteria for exclusion: optic disks larger than 4 mm(2), media opacities, patients younger than 33 years or older than 66 years. None of the subjects had earlier FDT perimetry. One eye of each patient and control subject entered the statistical evaluation. Database and statistical software were used for case-wise recalculation of all missed localized probability levels to create a FDT screening score., Results: At a predefined specificity of 94.5% in control eyes, discrimination between "perimetric" glaucoma and normal subjects is superior using the FDT perimetry (sensitivity = 84.8%) in comparison to polarimetry (sensitivity = 63.8%), whereas sensitivity is similar with both methods in "preperimetric" patients (GDx, FDT: 25.4%). In several cases, patients classified as glaucomatous by the GDx are not the same patients as identified by the FDT perimetry. Therefore, a two-dimensional discrimination analysis can increase correct positive classification. Using a linear combination of the present FDT screening score and polarimetry ("the number"), 92.4% of "perimetric" glaucoma eyes and 44.1% of "preperimetric" glaucoma eyes have been classified as glaucomatous., Conclusion: Joint usage of polarimetry and FDT perimetry indicate that a combination of different techniques which can uncover different glaucoma properties, might be helpful in early glaucoma detection.

Purpose: To report fragile histidine triad expression and microsatellite instability in periocular sebaceous gland carcinoma., Design: Interventional case series., Methods: Biopsy specimens of periocular sebaceous gland carcinoma obtained from six patients (mean age, 60 +/- 17 years; range, 38 to 83 years, 5 male, 1 female) with Muir-Torre syndrome and histopathologically proven sebaceous gland carcinoma were studied immunohistochemically for the presence of fragile histidine triad protein. Polymerase chain reaction-based analysis of the markers BAT25, BAT26, D2S123, D5S346, and D17S250 was performed for microsatellite instability in tumorous and matching normal tissues., Results: Fragile histidine triad protein was detectable in the sebaceous gland carcinoma from one patient with microsatellite instability. It was not detectable in sebaceous gland carcinoma specimens from five patients without any evidence of microsatellite instability., Conclusion: Inactivation of fragile histidine triad tumor suppressor gene or inactivation of the mismatch-repair system resulting in microsatellite instability may contribute to the development of periocular sebaceous gland carcinoma in Muir-Torre syndrome.

Purpose: To evaluate whether discriminant analysis formulas of optic disc variables measured by confocal laser scanning tomography can detect glaucomatous visual field defects, to compare the diagnostic precision of these formulas to detect glaucomatous visual field defects in different types of chronic open-angle glaucoma, and to assess whether gender or refractive error influence the results obtained by the formulas., Methods: One hundred and sixty-one patients with perimetrically defined glaucomatous optic nerve damage and 194 healthy subjects were recruited. All patients underwent confocal laser scanning tomography of the optic disc. The data were analyzed with three linear discriminant analysis formulas (sectorial, Bathija, and Mikelberg) obtained in sets of data different from those used in the present study., Results: The areas under the receiver-operating characteristic curves of the three formulas and of the cup shape measure as a single parameter ranged from 0.649 to 0.81 in the entire group, and the results did not change when age-matched eyes were considered (0.618-0.812). In each of the glaucoma subgroups with primary open-angle, pseudoexfoliative, and normal-pressure glaucoma, and additionally in the hyperopic, myopic, female, and male subgroups, the sectorial formula had the highest diagnostic precision and the highest correlation coefficients with the visual field indices, followed by the Bathija and Mikelberg formulas, without major differences between the subgroups. All three formulas were more effective than the cup shape measure as a single parameter., Conclusion: In the various chronic open-angle glaucomas, the sectorial and Bathija formulas tended to have higher diagnostic precision than the Mikelberg formula and the cup shape measure. Gender and refractive error do not markedly influence the diagnostic precision of the formulas tested. The scores of the formulas are mild indicators of the amount of glaucomatous visual field loss. All three formulas are superior to the single cup shape measure in the detection of glaucomatous optic nerve damage.

Purpose: Determination of lens opacity is important in aging glaucoma patients, because sensory testing may be influenced by increasing lens opacity. Purpose of this study was to measure lens opacity in normals and glaucoma patients using two different techniques, to compare both methods, and to correlate the results with contrast sensitivity testing., Methods: 94 glaucomatous eyes, 47 ocular hypertensive eyes, and 79 control eyes were studied using the following devices: opacity lens meter (OLM, objective back scatter method), stray light meter (SLM, subjective forward scatter using flicker light), and temporal contrast sensitivity (full-field flicker test). SLM results were separately analyzed at the lower and upper flicker disappearance. All subjects were younger than 66 years and had no significant cataracts., Results: In patients and in normal subjects OLM readings and SLM findings elicited at the upper disappearance point are significantly correlated with age and with each other (R >0.45, P<0.001), while SLM at the lower disappearance point shows no such correlation. In normals, but not in patients, SLM at the lower disappearance point is significantly correlated with temporal contrast sensitivity., Conclusions: Both devices can be used for quantifying lens opacity in glaucoma. SLM readings with increasing light intensity at the lower disappearance point seems to be more influenced by the individual flicker sensitivity than determination of the upper flicker disappearance. Therefore, using the SLM in glaucoma patients, the threshold measurements based on the upper disappearance of the flicker should be used instead of the suggested mean threshold measurements.

In the last decade, new imaging techniques have been added to conventional fundus photography and have been evaluated for use in early glaucoma. They all measure the loss of neuroretinal rim or retinal nerve fiber layer as a correlate to glaucomatous ganglion cell and axon loss. The value of optic disc photography, planimetry, laser scanning tomography, laser scanning polarimetry, and optical coherence tomography for the diagnosis of glaucomatous eyes in a preperimetric or early perimetric stage is analyzed on the basis of sensitivity, specificity, and receiver operating characteristics (ROC) curves. It becomes clear that all these techniques allow a more or less semi-automated evaluation of the optic disc and retinal nerve fiber layer but still have their limitations in the diagnosis of a very early, preperimetric stage of the glaucoma disease.

Background: Increased plasma galactitol levels may lead to development of bilateral pediatric cataract., Patient: A 3-year-old boy was found to suffer from a bilateral zonular cataract. Extracapsular lensectomy with posterior capsulotomy, transpupillar anterior vitrectomy and posterior chamber lens implantation were performed during a 4-month-interval., Results: The epimerase-activity in red cells of the index patient was found to be significantly decreased (11.2 mumol/h/g Hb; normal range; 19-35). From other family members, such as the brother (16.8), the father (16.0) and the grandfather (15.6), a diminished red cell activity was observed. The mother whose epimerase activity was considerably lower than that of the above mentioned family members (13.3) showed also a zonular bilateral cataract., Conclusions: Investigation of enzymes and polyols of galactose metabolism as well as consultation of the concerned families are recommended for clarification of cataract development.

Purpose: To review the clinicopathologic features, management and follow-up in five patients with periocular Merkel cell carcinoma (MCC)., Methods: In this case series study we reviewed the clinical records and histopathologic findings of five consecutive patients with MCC, treated and followed between May 1991 and November 1998., Results: Four patients were female and one was male. Their mean age at the time of surgery was 80 years (range: 69-86 years). Patients presented with a painless, nonulcerated, rapidly growing, solitary reddish or violaceous nodule, ranging in size from 11 to 21 mm, located in the upper eyelid in 4 patients and in the left eyebrow in one patient. Management included excision with frozen section control in three patients, and excision with wide surgical margins in two patients. Histopathologically, all tumors exhibited round cells of intermediate size and scanty cytoplasm, and large, round to oval vesicular nuclei with finely dispersed chromatin and one to three inconspicuous nucleoli. Mitotic figures were numerous. No patient had regional or extraregional metastases at diagnosis. Local recurrence or distant metastases were not detectable during a mean follow-up period of 45 months (range: 32-61 months). This outcome contrasts with the high incidence of local recurrence and early nodal metastasis reported in previous publications., Conclusions: Early diagnosis and aggressive, histologically controlled surgical treatment of this rare, highly malignant tumor may provide a longer disease-free period. Further investigation is necessary to determine the prognostic factors for recurrence and survival.

Purpose: To compare recovery of temporal contrast sensitivity after flicker stress between control subjects and patients with glaucoma., Methods: Forty-three patients with primary open-angle glaucoma and secondary open-angle or normal-tension glaucoma of the Erlangen Glaucoma Registry and 30 healthy control subjects had their temporal contrast sensitivity measured at 37 Hz and their recovery time determined after monocular exposure to 30 seconds of 58% contrast full-field flicker. Recovery time of temporal contrast sensitivity was measured as the time interval from cessation of flicker until twice the threshold value was reached., Results: Patients with glaucoma had a significant reduction in temporal contrast sensitivity (P < 0.001). Recovery time was also significantly longer in patients with glaucoma (23.8 +/- 24.1 seconds) than in control subjects (7.6 +/- 2.6 seconds; P < 0.001). There was a significant positive correlation between recovery time and mean visual field defect (0.5; P < 0.001) and a significant negative correlation between recovery time and neuroretinal rim area of the optic disc (0.32; P = 0.04)., Conclusions: Recovery of temporal contrast sensitivity after flicker stress is impaired in some patients with glaucoma. This might be the result of functional impairment of the inner retina, outer retina, or both in glaucoma.

Purpose: To determine the influence of lens opacities on temporal contrast sensitivity, measured by the full-field flicker test ("Erlangen flicker test")., Methods: Thirty-six consecutive patients (mean age 71.1+/-11.6 years, 12 male, 24 female, refractive error -1.5+/-3.8 dpt) with cataract (visual acuity 0.21+/-0.16, retinal acuity 0.56+/-0.32, no glaucoma) were studied. Temporal contrast sensitivity (full-field flicker test, 37.1 Hz) and lens opacity (back scatter Lens Opacity Meter, Interzeag) were measured preoperatively and on the 3rd postoperative day., Statistics: nonparametric tests (Wilcoxon-test, Spearman correlation coefficient, Mann-Whitney U-test)., Results: No significant difference was seen in temporal contrast sensitivity pre- and postoperatively, but there was a significant difference in lens opacity measurements pre- and postoperatively. No significant correlation was found between temporal contrast sensitivity and lens opacity values preoperatively and postoperatively., Conclusion: The temporal contrast sensitivity, measured by the full-field flicker test, seems to be independent of lens opacity due to the range of cataract included in this study. The data indicate that the full-field flicker test is useful for early glaucoma detection even in patients with cataract formations.

Background: A study was performed to evaluate whether visual field analysis using a perimetric nerve fiber bundle map gives information additional to global visual field indices and cumulative defect curves for early glaucoma diagnosis., Methods: One hundred and four control subjects, 124 patients with ocular hypertension (OHT), 97 patients with high-tension glaucoma without visual field defects (preHTG) and 91 patients with open-angle glaucoma with visual field defects [30 low-tension glaucoma (LTG), 61 high-tension glaucoma (HTG)] were included in this study. Correlation analyses were performed between (a) global visual field indices and total neuroretinal rim (NRR) area; (b) local mean values of four visual field areas and the NRR area of the corresponding four optic disk sectors; and (c) local mean values of 10 perimetric nerve fiber bundles (PNFB 1-10) according to Weber and Ulrich (1991) and the four optic disk sectors. The correlations were adjusted for global mean defect and total NRR., Results: There were no significant correlations between NRR area and visual field in control subjects or in patients with OHT or preHTG for all three analyses. Significant correlations were found between the global visual field indices and the total NRR area for LTG and HTG. Significant correlations between local mean defects and NRR area of corresponding optic disk sectors were found only in LTG for the superior and inferior visual field area and the PNFB covering these areas., Conclusion: The method used for visual field analysis and sectorization of the optic disk does not give additional information on visual field defects in patients with normal global visual field indices and a normal cumulative defect curve. The nerve fiber bundle-related visual field analysis allows the topographical determination and quantification of glaucomatous damage.