Anselm Juenemann

Retinal nerve fiber layer thickness in normals measured by spectral domain OCT.

PurposeTo determine normal values for peripapillary retinal nerve fiber layer thickness (RNFL) measured by spectral domain Optical Coherence Tomography (SOCT) in healthy white adults and to examine the relationship of RNFL with age, gender, and clinical variables. Patients and MethodsThe peripapillary RNFL of 170 healthy patients (96 males and 74 females, age 20 to 78 y) was imaged with a high-resolution SOCT (Spectralis HRA+OCT, Heidelberg Engineering) in an observational cross-sectional study. RNFL thickness was measured around the optic nerve head using 16 automatically averaged, consecutive circular B-scans with 3.4-mm diameter. The automatically segmented RNFL thickness was divided into 32 segments (11.25 degrees each). One randomly selected eye per subject entered the study. ResultsMean RNFL thickness in the study population was 97.2±9.7 &mgr;m. Mean RNFL thickness was significantly negatively correlated with age (r=−0.214, P=0.005), mean RNFL decrease per decade was 1.90 &mgr;m. As age dependency was different in different segments, age-correction of RNFL values was made for all segments separately. Age-adjusted RNFL thickness showed a significant correlation with axial length (r=−0.391, P=0.001) and with refractive error (r=0.396, P<0.001), but not with disc size (r=0.124). ConclusionsNormal RNFL results with SOCT are comparable to those reported with time-domain OCT. In accordance with the literature on other devices, RNFL thickness measured with SOCT was significantly correlated with age and axial length. For creating a normative database of SOCT RNFL values have to be age adjusted.

Longitudinal analysis of progression in glaucoma using spectral-domain optical coherence tomography.

PURPOSE To compare the longitudinal loss of RNFL thickness measurements by SD-OCT in healthy individuals and glaucoma patients with or without progression concerning optic disc morphology. METHODS A total of 62 eyes, comprising 38 glaucomatous eyes with open angle glaucoma and 24 healthy controls, were included in the study (Erlangen Glaucoma Registry, NTC00494923). All patients were investigated annually over a period of 3 years by Spectralis SD-OCT measuring peripapillary RNFL thickness. By masked comparative analysis of photographs, the eyes were classified into nonprogressive and progressive glaucoma cases. Longitudinal loss of RNFL thickness was compared with morphological changes of optic disc morphology. RESULTS Mixed model analysis of annual OCT scans revealed an estimated annual decrease of the RNFL thickness by 2.12 μm in glaucoma eyes with progression, whereas glaucoma eyes without progression in optic disc morphology lost 1.18 μm per year in RNFL thickness (P = 0.002). The rate of change in healthy eyes was 0.60 μm and thereby also significantly lower than in glaucoma eyes with progression (P < 0.001). The intrasession variability of three successive measurements without head repositioning was 1.5 ± 0.7 μm. The loss of mean RNFL thickness exceeded the intrasession variability in 60% of nonprogressive eyes, and in 85% of progressive eyes after 3 years. CONCLUSIONS LONGITUDINAL MEASUREMENTS OF RNFL THICKNESS USING SD-OCT SHOW A MORE PRONOUNCED REDUCTION OF RNFL THICKNESS IN PATIENTS WITH PROGRESSION COMPARED WITH PATIENTS WITHOUT PROGRESSION IN GLAUCOMATOUS OPTIC DISC CHANGES. (www.clinicaltrials.gov number, NTC00494923.).

Regulation of lysyl oxidase-like 1 (LOXL1) and elastin-related genes by pathogenic factors associated with pseudoexfoliation syndrome.

PURPOSE Pseudoexfoliation (PEX) syndrome/glaucoma is a complex, late-onset disorder of the elastic fiber system. Strong genetic risk is conferred by the lysyl oxidase-like 1 (LOXL1) gene, but additional comodulating factors are necessary for the manifestation of the disease. The aim of this study was to analyze the effect of various PEX-associated pathogenic factors on the genotype-correlated expression of LOXL1 and elastin-related genes. METHODS Cultured human Tenons capsule fibroblasts with high- and low-risk LOXL1 haplotypes were exposed to transforming growth factor (TGF)-β1, interleukin (IL)-6, homocysteine, oxidative stress, hypoxia, or ultraviolet (UV) radiation. Changes in the expression of LOXL1 and elastic constituents of PEX material and TGF-β1 were assessed by quantitative real-time PCR, Western blotting, immunohistochemistry, and electron microscopy. RESULTS Treatment of fibroblasts with TGF-β1, oxidative stress, UV light, and hypoxia induced a significant increase in expression levels of LOXL1 and elastic proteins, whereas the effect of IL-6 was limited to induction of elastic constituents. Immunohistochemistry and electron microscopy confirmed an upregulation of LOXL1 and elastic fiber proteins and their assembly into extracellular microfibrillar networks with focal aggregation of microfibrils into PEX-like fibrils on stimulation with TGF-β1 and oxidative stress. Basal and stimulated expression of LOXL1 mRNA and protein was slightly decreased in cells carrying the high-risk compared with the low-risk haplotype of LOXL1, but the differences between groups were statistically not significant. CONCLUSIONS The findings support the notion that both genetic and nongenetic fibrogenic factors, particularly TGF-β1 and oxidative stress, may cooperate in the stable accumulation of PEX aggregates.

Comparison of scanning laser polarimetry and optical coherence tomography in quantitative retinal nerve fiber assessment.

PurposeTo investigate the relationship between retinal nerve fiber layer (RNFL) measurements in corresponding areas obtained with scanning laser polarimetry and optical coherence tomography and to compare their discriminating ability in the diagnosis of preperimetric and perimetric glaucoma. Patients and MethodsThree hundred eighty-six subjects—57 healthy controls, 145 ocular hypertensive patients, 89 with preperimetric glaucoma, and 95 with perimetric glaucoma—were recruited from the Erlangen Glaucoma Registry. Perimetry, 24-hours intraocular pressure profile, stereographic optic disc slides, optical coherence tomography StratusOCT, and scanning laser polarimetry GDx VCC (Carl Zeiss Meditec, Inc, Dublin, CA) were performed in all patients. Receiver operating characteristic (ROC) curves were constructed for mean RNFL values, sector data, and indices. Sensitivity was estimated at ≥90% and ≥80% of specificity to compare the discriminating ability of each imaging modality. ResultsFor discrimination between glaucomatous and healthy eyes in GDx VCC the nerve fiber index demonstrated the largest area under the ROC curve (AUROC) (0.962±0.013), whereas in StratusOCT the largest AUROC (0.986±0.006) was found in the inferior quadrant. For preperimetric glaucoma detection the nerve fiber index achieved the largest AUROC (0.783±0.037). In contrast, the total RNFL average obtained using StratusOCT showed the largest AUROC (0.904±0.025). Bland-Altman plots showed good agreement between both instruments. ConclusionsBoth the GDx VCC and StratusOCT demonstrate increasing RNFL loss with advanced glaucomatous damage and were comparable in the diagnosis of perimetric glaucoma. Preperimetric glaucomatous damage may be better assessed by StratusOCT.

Visualization of changes of the iris configuration after peripheral laser iridotomy in primary melanin dispersion syndrome using optical coherence tomography.

Pigment or melanin dispersion syndrome is characterized by radial iris transillumination defects, retrocorneal Krukenberg spindle, and dense trabecular pigmentation. Reverse pupillary block has been presumed as one possible pathogenetic mechanism for backward bowing of the iris leading to iris-zonular rubbing and distribution of melanin granules in the anterior chamber. Laser iridotomy is recommended as a treatment to prevent further melanin dispersion and development of pigmentary glaucoma. The effect of Nd:YAG laser iridotomy as a prophylactic and potentially causal treatment in melanin dispersion syndrome can be easily visualized by optical coherence tomography as a fast and noncontact procedure.

M-charts as a tool for quantifying metamorphopsia in age-related macular degeneration treated with the bevacizumab injections

BackgroundThis article is aimed to assess quantitatively metamorphopsia using M-charts in patients suffering from wet age-related macular degeneration (AMD) treated with the intravitreal bevacizumab injections and to compare the results with traditional Amsler grid and ocular coherence tomography (OCT).MethodsThirty-six patients diagnosed with wet AMD were examined one day before and one month after the intraocular injection of bevacizumab. Horizontal and vertical metamorphopsia scores using M-charts, distance visual acuity, Amsler test and OCT were performed at each visit. Additionally, 23 healthy subjects were examined as a control group.ResultsThe rate of metamorphopsia detection was 89% with M-charts and 69% with Amsler test. The horizontal metamorphopsia score improved in 22 patients, the vertical metamorphopsia score improved in 16 patients, the Amsler grid results improved in 6 patients, visual acuity improved in 17 patients. There was no correlation between the degree of metamorphopsia and the visual acuity or the central retinal thickness (CRT). The specificity of both the M-charts and Amsler grid was 100%.ConclusionsThe rate of metamorphopsia detection in wet AMD patients was better with M-charts than with Amsler grid. M-charts may be used in the assessment of efficacy of treatment with intravitreal bevacizumab injections as another outcome measure, moreover they can be used even at home for the self-assessment. M-charts provide additional information concerning the visual function, independent of the visual acuity, CRT and morphological changes in OCT.

Unilateral retinitis pigmentosa: 30 years follow-up.

This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa (RP), who presented first in 1984 at the age of 43 years. At the beginning, there were cells in the vitreous leading to the diagnosis of uveitis with vasculitis. Within 30 years, the complete clinical manifestation of RP developed with bone spicule-shaped pigment deposits, pale optic disc, narrowed arterioles, cystoid macular oedema, posterior subcapsular cataract, concentric narrowing of the visual field and undetectable electroretinogram signal. At the age of 72 years, there are still no signs of retinal dystrophy in the other eye.

Content of Kynurenic Acid and Activity of Kynurenine Aminotransferases in Mammalian Eyes

The present study investigated the kynurenic acid (KYNA) contents and kynurenine aminotransferase (KAT I and II) activity in structures of the human, monkey, rabbit and bovine eye. KYNA levels were investigated with HPLC and detected fluorimetrically. The activity of KAT I and II was assayed as quantitative analysis of newly synthesized KYNA in vitro. Mean KYNA levels (±SD) in the human retina and vitreous body were 36.8 ± 7.6 and 33.1 ± 6.2 pmol/g wet tissue weight, respectively. In human eyes, KAT I activity in the vitreous body was 0.57 ± 0.28, that of KAT II was 2.56 ± 0.69. KAT I activity in the retina was 3.42 ± 1.17 and that of KAT II 10.75 ± 9.2. (KAT activity is expressed as KYNA synthesis in picomoles per gram wet tissue weight per hour.) The values of KYNA and KAT observed in other mammalian species tested were in the same range. In conclusion, KYNA and KAT enzymatic activity are present in the structures of human and other mammalian eyes.

Influence of glaucomatous damage and optic disc size on glaucoma detection by scanning laser tomography.

PurposeTo investigate the impact of glaucomatous damage and optic disc size on different automated Heidelberg Retina Tomograph classifications for discriminating glaucoma and healthy controls. Patients and MethodsTwo hundred seventy-three glaucoma patients and 276 healthy controls were recruited from the Erlangen Glaucoma Registry. Standard static white on white perimetry, 24-hour intraocular pressure profile, stereographic optic disc slides, and scanning laser tomography were performed in all patients and controls. The effect of glaucoma stage and disc size on the diagnostic accuracy was evaluated using receiver operating characteristic curves. Results of the Glaucoma Probability Score were compared with other recently described multivariate classifications. ResultsAreas under the receiver operating characteristic curves for discrimination between glaucoma and healthy eyes of the overall classification by Glaucoma Probability Score, Moorfields regression analysis, Bathija, Iester, Mikelberg, and Mardin increased from 0.71, 0.65, 0.70, 0.67, 0.65, and 0.63 for early glaucoma (Jonas: stage I) to 0.96, 0.95, 0.94, 0.94, 0.92, and 0.88 for advanced glaucomatous damage (Jonas: stage IV). Best performance of discrimination between glaucoma and healthy eyes using area under the receiver operating characteristic curves were observed for medium-sized discs (2.1 to 2.49 mm2) and worst performance for large optic discs (>3.1 mm2). Glaucoma Probability Score classification was superior to other investigated classifications in most of the investigated subgroups. ConclusionsThe diagnostic accuracy of all classifications depends on the optic disc size and the glaucoma stage. Glaucoma Probability Score showed a better diagnostic performance than Moorfields regression analysis and was similar to that of Bathija.

Plasma homocysteine levels in patients with normal tension glaucoma.

PurposeTo investigate whether there is an association of elevated plasma levels of homocysteine (Hcy) and normal tension glaucoma (NTG). Patients and MethodsPlasma levels of Hcy (fluorescence polarization immunoassay), vitamin B6 (high-performance liquid chromatography), vitamin B12, and folate levels (immunoassay) were determined in 42 patients with NTG and in 42 age-matched and sex-matched controls. ResultsNo significant difference regarding Hcy (NTG: 10.95 &mgr;mol/L±2.65; controls: 11.29 &mgr;mol/L±2.76) (P=0.639), vitamin B6 (NTG: 14.45 ng/mL±12.89; controls: 13.57 ng/mL±10.41) (P=0.629), vitamin B12 (NTG: 387.73 pg/mL±282.04; controls: 423.27 pg/mL±188.85) (P=0.052) and folate (NTG: 9.45ng/mL±3.42; controls: 10.82 ng/mL±4.48) (P=0.181) levels were found between both groups. ConclusionsAn association of elevated Hcy levels and NTG was not found and therefore a role of Hcy as a modifiable risk factor in the pathogenesis of NTG seems unlikely.