Esther M. Hoffmann

Diagnostic ability of retinal ganglion cell complex, retinal nerve fiber layer, and optic nerve head measurements by Fourier-domain optical coherence tomography

PurposeTo evaluate the diagnostic ability of Fourier-domain optical coherence tomography (FD-OCT) measurements in glaucoma patients, patients with ocular hypertension, and normal subjects.MethodsNinety-three participants with open-angle glaucoma (OAG), 58 patients with ocular hypertension (OHT), and 60 healthy control subjects were included in the study. All study participants underwent FD-OCT imaging. Retinal ganglion cell complex (GCC), macular thickness, peripapillary retinal nerve fiber layer thickness (RFNL), and optic nerve head parameters (ONH) were measured in each participant. The diagnostic ability was evaluated using area under the receiver operating characteristics curves (AUROC).ResultsGlaucoma patients showed a significant reduction in GCC and macular retinal thickness compared to patients with OHT and normal subjects. No differences in GCC were found between the patients with OHT and normal subjects. The best diagnostic ability in the comparison between glaucoma and normal subjects after adjusting for age was found for cup-to-disc ratio (AUROC = 0.848), RNFL average thickness (AUROC = 0.828), and GCC global loss volume (AUROC = 0.805). The diagnostic power of the best GCC, RNFL, and ONH parameter did not show differences beyond random variation (p > 0.05).ConclusionsImaging of the GCC using FD-OCT (RTVue-100) has a comparable diagnostic ability to RNFL and ONH measurements in distinguishing between glaucoma patients and healthy subjects. No differences were found between patients with OHT and normal subjects with regard to ONH, RNFL, and GCC parameters.

Intraocular pressure and ocular pulse amplitude using dynamic contour tonometry and contact lens tonometry

BackgroundThe new Ocular Dynamic Contour Tonometer (DCT), investigational device supplied by SMT (Swiss Microtechnology AG, Switzerland) allows simultaneous recording of intraocular pressure (IOP) and ocular pulse amplitude (OPA). It was the aim of this study to compare the IOP results of this new device with Goldmann tonometry. Furthermore, IOP and OPA measured with the new slitlamp-mounted DCT were compared to the IOP and OPA measured with the hand-held SmartLens®, a gonioscopic contact lens tonometer (ODC Ophthalmic Development Company AG, Switzerland).MethodsNineteen healthy subjects were included in this study. IOP was determined by three consecutive measurements with each of the DCT, SmartLens®, and Goldmann tonometer. Furthermore, OPA was measured three times consecutively by DCT and SmartLens®.ResultsNo difference (P = 0.09) was found between the IOP values by means of DCT (mean: 16.6 mm Hg, median: 15.33 mm Hg, SD: +/- 4.04 mm Hg) and Goldmann tonometry (mean: 16.17 mm Hg, median: 15.33 mm Hg, SD: +/- 4.03 mm Hg). The IOP values of SmartLens® (mean: 20.25 mm Hg, median: 19.00 mm Hg, SD: +/- 4.96 mm Hg) were significantly higher (P = 0.0008) both from Goldmann tonometry and DCT. The OPA values of the DCT (mean: 3.08 mm Hg, SD: +/- 0.92 mm Hg) were significantly lower (P = 0.0003) than those obtained by SmartLens® (mean: 3.92 mm Hg, SD: +/- 0.83 mm Hg).ConclusionsDCT was equivalent to Goldmann applanation tonometry in measurement of IOP in a small group of normal subjects. In contrast, SmartLens® (contact lens tonometry) gave IOP readings that were significantly higher compared with Goldmann applanation tonometer readings. Both devices, DCT and SmartLens® provide the measurement of OPA which could be helpful e.g. for the management of glaucoma.

Comparison of the new perimetric GATE strategy with conventional full-threshold and SITA standard strategies

PURPOSE A new, fast-threshold strategy, German Adaptive Thresholding Estimation (GATE/GATE-i), is compared to the full-threshold (FT) staircase and the Swedish Interactive Thresholding Algorithm (SITA) Standard strategies. GATE-i is performed in the initial examination and GATE refers to the results in subsequent examinations. METHODS Sixty subjects were recruited for participation in the study: 40 with manifest glaucoma, 10 with suspected glaucoma, and 10 with ocular hypertension. The subjects were evaluated by each threshold strategy on two separate sessions within 14 days in a randomized block design. RESULTS SITA standard, GATE-i, and GATE thresholds were 1.2, 0.6, and 0.0 dB higher than FT. The SITA standard tended to have lower thresholds than those of FT, GATE-i, and GATE for the more positive thresholds, and also in the five seed locations. For FT, GATE-i, GATE, and SITA Standard, the standard deviations of thresholds between sessions were, respectively, 3.9, 4.5, 4.2, and 3.1 dB, test-retest reliabilities (Spearmans rank correlations) were 0.84, 0.76, 0.79, and 0.71, test-retest agreements as measured by the 95% reference interval of differences were -7.69 to 7.69, -8.76 to 9.00, -8.40 to 8.56, and -7.01 to 7.44 dB, and examination durations were 9.0, 5.7, 4.7, and 5.6 minutes. The test duration for SITA Standard increased with increasing glaucomatous loss. CONCLUSIONS The GATE algorithm achieves thresholds that are similar to those of FT and SITA Standard, with comparable accuracy, test-retest reliability, but with a shorter test duration than FT.

Structure-function relationship between FDF, FDT, SAP, and scanning laser ophthalmoscopy in glaucoma patients.

PURPOSE Flicker defined form perimetry (FDF) and frequency doubling technology perimetry (FDT) are alleged to detect glaucoma at an earlier stage than standard automated perimetry (SAP). It is the purpose of this study to investigate the structure-function relationship between FDF, FDT, SAP, and confocal scanning laser ophthalmoscopy (cSLO) in patients with glaucoma. METHODS Seventy-six patients with glaucoma were included in the study. Patients were tested with SAP, Matrix-FDT, FDF perimetry, and cSLO. Structure-function relationships between global and sectoral cSLO parameters and global and sectoral mean sensitivity (MS) of SAP, Matrix-FDT, and FDF were calculated using Spearmans rank correlation and linear regression. RESULTS Overall, FDF perimetry showed the strongest structure-function relationship (GLOBAL correlation with rim area: 0.44; range of significant sectoral FDF values: 0.23-0.69), followed by FDT (global correlation with rim area: 0.35; range of significant sectoral FDT values: 0.25-0.60). SAP presented with the weakest structure-function relationship and fewer statistically significant results (global correlation with rim volume: 0.32; range of significant sectoral SAP values: 0.23-0.58). Sector-by-sector, the structure-function relationship was greatest in the superotemporal and inferotemporal regions. Weakest correlations were found in the inferonasal and nasal sectors. CONCLUSIONS The correlation between structure and function is stronger in FDF and FDT compared with SAP. Correlations are strongest in temporal areas where glaucomatous damage tends to occur first. A better understanding of the structure-function relationship should allow for improved detection and management of glaucoma patients.

Distribution of Intraocular Pressure and Its Association with Ocular Features and Cardiovascular Risk Factors: The Gutenberg Health Study

PURPOSE To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort. DESIGN Population-based, cross-sectional study. PARTICIPANTS This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment. METHODS Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visual field testing; and a thorough general examination focused on cardiovascular parameters, psychological evaluation, and laboratory tests, including genetic analysis. MAIN OUTCOME MEASURES Mean and reference interval of IOP stratified by age, gender, and eye. RESULTS Mean ± standard deviation (SD) IOP was 14.0 ± 2.6 mmHg in both eyes, 13.9 ± 2.7 mmHg in right eyes, and 14.0 ± 2.7 mmHg in left eyes. Mean ± SD IOP in men (n = 2216) and in women (n = 2119) was 14.1 ± 2.7 mmHg and 13.9 ± 2.5 mmHg with an intersex difference (P = 0.009). Positive univariate associations with higher IOP were detected for brown iris color, central corneal thickness, hypertension, diabetes, smoking, obesity, dyslipidemia, body mass index, weight, hip size (women only), waist circumference, and waist-to-hip ratio. Multivariate testing revealed male gender, central corneal thickness, brown iris color, hypertension, smoking, and waist-to-hip ratio to be correlated with higher IOP. In women, age correlated negatively with IOP in the multivariate analysis. CONCLUSIONS Intraocular pressure distribution in this cohort yielded a lower mean IOP than in similar white study populations. Increasing age in women correlated with lower IOP. Association analyses with several systemic characteristics revealed that cardiovascular risk factors correlated with higher IOP. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Irregularity of the posterior corneal surface after curved interface femtosecond laser-assisted versus microkeratome-assisted descemet stripping automated endothelial keratoplasty.

Purpose: During donor tissue preparation for Descemet stripping automated endothelial keratoplasty (DSAEK), either microkeratome or femtosecond laser can be used for intrastromal cutting. We compared morphological and functional outcomes after DSAEK using both cutting techniques. Methods: In this retrospective study, 22 uneventful DSAEK surgeries were reviewed. Eight donor corneas were prepared for DSAEK using the VisuMax femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). Fourteen corneas were processed using an Amadeus II microkeratome (Ziemer Ophthalmic Systems AG, Port, Switzerland). The postoperative best spectacle-corrected visual acuity was measured. Furthermore, corneal optical coherence tomography scans (RTVue; Optovue, Fremont, CA) were conducted and analyzed for graft cornea thickness and posterior surface irregularities using regression analysis (SPSS; IBM, Chicago, IL) on a second-order polynomial curve as a model for the posterior surface. Results: The graft thickness was 166.3 ± 58.2 &mgr;m (mean ± SD) in the femtosecond laser group and 172.7 ± 48.2 &mgr;m in the microkeratome group. The best-corrected visual acuity of 0.48 ± 0.20 (logarithm of the minimum angle of resolution) in the femtosecond laser group was significantly poorer when compared with 0.33 ± 0.11 in the microkeratome group (P = 0.038). Moreover, the root mean square error between the posterior corneal surface and an ideal parabola surface was significantly higher in the femtosecond laser group (9.9 ± 2.2 &mgr;m) than in the microkeratome group (5.7 ± 2.2 &mgr;m; P < 0.001). Conclusions: Our study underlines the current superiority of a microkeratome-assisted preparation of the stromal–endothelial lamella before DSAEK surgery compared with the curved interface femtosecond laser-assisted processing.

Reproducibility of ocular response analyzer measurements and their correlation with central corneal thickness

BackgroundTo evaluate the inter- and intraobserver variability of ocular response analyzer (ORA) measurements, namely corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH).MethodsOne randomly chosen eye of 46 healthy volunteers was included in this study. Three clinical observers performed three consecutive measurements using ORA, with an interval of 1–2 minutes between measurements. In all subjects, central corneal thickness (CCT) was measured. The inter- and intraobserver reproducibility for IOPcc, CRF and CH was assessed by ANOVA-based intraclass correlation coefficient (ICC) and coefficient of variation (CV).ResultsThe mean ICC for interobserver reproducibility was 0.94 for IOPcc, 0.90 for CRF, and 0.86 for CH. The corresponding CV values were 12.8%, 10.3%, and 13.6% respectively. The intraobserver ICC values for IOPcc were 0.86 for the first examiner, 0.84 for the second, and 0.89 for the third. CV was 11.7%, 11.9%, and 11.0% respectively. For CRF, the intraobserver ICC values were 0.69, 0.81, and 0.63, and corresponding CV values were 9.6%, 8.1, and 10.8%. The intraobserver ICC for CH was 0.66 for the first observer, 0.71 for the second, and 0.61 for the third examiner. The respective CV values were 12.7%, 11.8%, and 13.9%. There was a significant correlation between CCT and CRF (Rsq = 0.13, p = 0.02). The correlations of CCT with IOPcc and CH were not significant (p > 0.05).ConclusionsThe interobserver reproducibility of ORA measurements was almost perfect for IOPcc, CRF, and CH. The intraobserver short-term reproducibility was almost perfect for IOPcc and substantial for CRF and CH, for all observers. The significant correlation between CCT and CRF, and no association between IOPcc and CCT, are in agreement with previous studies. There was no significant correlation between CH and CCT in our study. This device might be useful in glaucoma diagnosis and management.

Distribution of central corneal thickness and its association with ocular parameters in a large central European cohort: the Gutenberg health study.

Main objective To evaluate the distribution of central corneal thickness (CCT) in a large German cohort and to analyse its relationship with intraocular pressure and further ocular factors. Design Population-based, prospective, cohort study. Methods The Gutenberg Health Study (GHS) cohort included 4,698 eligible enrollees of 5,000 subjects (age range 35–74 years) who participated in the survey from 2007 to 2008. All participants underwent an ophthalmological examination including slitlamp biomicroscopy, intraocular pressure measurement, central corneal thickness measurement, fundus examination, and were given a questionnaire regarding glaucoma history. Furthermore, all subjects underwent fundus photography and visual field testing using frequency doubling perimetry. Results Mean CCT was 557.3±34.3 µm (male) and 551.6±35.2 µm in female subjects (Mean CCT from right and left eyes). Younger male participants (35–44 years) presented slightly thicker CCT than those older. We noted a significant CCT difference of 4 µm between right and left eyes, but a high correlation between eyes (Wilcoxon test for related samples: p<0.0001). Univariable linear regression stratified by gender showed that IOP was correlated with CCT (p<0.0001). A 10 µm increase in CCT led to an increase in IOP between 0.35–0.38 mm Hg, depending on the eye and gender. Multivariable linear regression analysis revealed correlations between gender, spherical equivalent (right eyes), and CCT (p<.0001 and p = 0.03, respectively). Conclusions We observed positive correlations between CCT and IOP and gender. CCT was not correlated with age, contact lens wear, positive family history for glaucoma, lens status, or iris colour.

Learning Curve and Fatigue Effect of Flicker Defined Form Perimetry

PURPOSE To evaluate the learning curve and fatigue effect of flicker defined form (FDF) perimetry. DESIGN Prospective cross-sectional study. MATERIAL AND METHODS One hundred forty-one eyes of 75 healthy subjects were included in the study. Every subject was measured 3 times on 3 different days within 3 months. Differences among the tests were analyzed for mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), reliability indices, test duration, and test points <5% and <0.5% in 75 right eyes on the basis of linear mixed models for repeated measurements. To assess the effect of fatigue, differences of MS, MD, and PSD values between 66 left and right eyes were evaluated regarding alterations between these 3 examinations. RESULTS After 3 test sessions, significant improvements were found in MS and MD among all 3 tests (P ≤ .01), and in PSD between test 1 and test 3 (P = .02). Test duration decreased significantly between tests 1 and 3 (P = .01); fixation-loss errors decreased significantly between tests 2 and 3 and between tests 1 and 3 (P = .02, respectively). Test points with p < 0.5% decreased significantly between tests 1 and 2 (P = .04) and 1 and 3 (P = .01) When comparing both eyes, MS, MD, and PSD were significantly better in first than in second eyes examined. CONCLUSIONS There exist significant learning and fatigue effects for repeated flicker defined form perimetry. For good and reliable results on FDF perimetry, at least 3 tests should be performed in an individual. Between the tests of both eyes, a rest should be offered.

Neuroprotection of medical IOP-lowering therapy

Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α2-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α2-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α2-adrenergic receptor agonist, brimonidine.