Agreement Analysis on Angle Characteristics With Automated Gonioscopy.

PRCIS: Automated gonioscopy is a recent method of recording angle pictures. Our study shows that agreement between observers is moderate in most categories used in clinical practice, underlying its clinical usefulness but also room for improvement. INTRODUCTION: Iridocorneal angle (ICA) imaging methods have been recently developed to record gonioscopic images. The purpose of this study was to perform an interrater agreement analysis of ICA photographs. METHODS: Multicentric cross-sectional observational study. Consecutive patients in 2 ophthalmology departments underwent automated gonioscopy. One picture per quadrant from each eye was selected for randomization. Pictures were graded and analyzed by 4 masked glaucoma specialists regarding angle opening, width, Shaffer and Spaeth gradings and other findings. Fleiss' κ statistics was performed to assess interrater agreement. RESULTS: A total of 50 patients were recruited, with the sample containing a variety of diagnosis including pseudoexfoliation (22%), angle-closure suspect (12%), and pigmentary glaucoma (4%). The sample included phakic (68%) and pseudophakic patients, as well as cases with gonio-implanted surgical devices (10%). There was moderate agreement on angle opening, angle width, presence of angle vessels, and peripheral anterior synechiae (κ=0.435, 0.511, 0.558, 0.488, respectively; P<0.01). Fair agreement was observed regarding Shaffer grading, site of iris root insertion, angle pigmentation features, and the presence of iris processes. Expectedly from a 2-dimensional picture, the configuration of peripheral iris was found to have a poor agreement. Subset analysis on higher quality pictures seemed to improve agreement on pigment but did not further improve on the overall good agreement on angle opening status. CONCLUSIONS: Our study shows that automated gonioscopy provides moderate agreement on most clinically relevant features. Binary characteristics such as angle opening or PAS seem to be more robust than more complex angle classification parameters.

The influence of electromagnetic radiation on the measurement behaviour of the triggerfish® contact lens sensor.

BACKGROUND: To assess a possible signal drift, noise and influences of electromagnetic radiation on the measurement behaviour of the Triggerfish® contact lens sensor, which might be mistaken as IOP fluctuations. METHODS: Contact lens sensors (Triggerfish®, SENSIMED AG, Lausanne, Switzerland) were fixed in a water bath. To reduce any external electromagnetic impulses, all plugs were removed from the sockets, no lights were switched on and no electronic devices, except a temperature logger were left in the test room. For 24 h signal drift, noise and the influences of a cordless telephone (Ascom d43 DECT Handset, EU DECT 1880-1900 MHz, Ascom Wireless, Baar, Switzerland), a smartphone (Sony Xperia Go ST27i, Sony Corporation, Tokyo, Japan) and a computer (Hewlett-Packard ProBook 650 15,6″ - D9S33AV, Hewlett-Packard Inc., Palo Alto, USA) on the measuring profile were analysed. RESULTS: Twenty-four-hour measurements without provoked external electromagnetic impulses yielded a profile without any signal drift and 8.2 mV eq noise. During the activation of the cordless telephone a maximum measurement variation of 3.2 mV eq. (4.1-7.3), smartphone 1.8 mV eq. (4.7-6.5) and computer 1.4 mV eq. (6.3-7.7) were observed. CONCLUSIONS: During 24-h measurements there was no signal drift and a very low noise. Patients concerned about electronic devices possibly interfering with the measurements of the contact lens sensor, can be informed, that the use of their cordless telephone, smartphone or computer does not cause any problems. The amount of the signal noise might help to define actual IOP fluctuations. Temperature fluctuations might influence the measuring profile.

[Do We Perform Glaucoma Surgery too Late?] / Operieren wir die Glaukome zu spät?

As glaucoma specialists, we often ask ourselves why patients are referred so late for surgery. Usually the patient is referred in a far advanced stage of the disease after long-term conventional treatment with topical medications. By that time, substantial morphologic damage is present and the patient is disabled by far advanced visual field defects. In addition, decompensated intraocular pressure, despite maximal tolerated medical treatment, is seen. Delayed surgery due to late diagnosis is rather a rare event. Various reasons may be responsible for this late referral. Improved IOP-lowering medications (i.e., fixed combinations), personal aversion (fear and knowledge of lack of improvement in visual acuity) against surgery, and imperfect glaucoma procedures may play an important role. A retrospective review of the last 274 cases referred for filtering glaucoma surgery is used to describe and analyze criteria for adequate timing of glaucoma surgery. This study reveals that almost ¾ of patients are referred rather late for glaucoma surgery. Criteria for adequate timing of glaucoma surgery are given for non-glaucoma specialists in particular. They apply for all types of glaucoma surgery, and the pros and cons are discussed in detail. Trabeculectomy is still regarded as the gold standard of glaucoma surgery. Because trabeculectomy may not be an ideal glaucoma procedure, there is hope that the modern less-invasive glaucoma procedures (MIGS) will be able to extend indications for glaucoma surgery. This may also lower the hurdle of referral for glaucoma surgery for both patients and non-glaucoma specialist doctors.

Measurement of tumor necrosis factor-alpha, interleukin-6, Fas ligand, interleukin-1α, and interleukin-1ß in the aqueous humor of patients with open angle glaucoma using multiplex bead analysis.

PURPOSE: Various cytokines, including tumor necrosis factor-alpha (TNF-α), Fas ligand (FasL), interleukin-1α (IL-1α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), contribute to the pathogenesis of primary open angle glaucoma (POAG). The present study was set to measure these cytokines in the aqueous humor of patients with POAG and in control subjects using multiplex bead analysis. METHODS: Twenty-five patients with POAG and 29 control subjects were enrolled in this case-control study. Aqueous humor concentrations of the cytokines (IL-1 α, IL-1 ß, IL-6, FasL, and TNF- α) were measured using multiplex bead analysis. RESULTS: Mean aqueous humor levels of IL-6 were significantly lower in patients with POAG compared to the control subjects (9.3±23.7 versus 55.3±94.4 pg/ml; p=0.002). No significant difference in the aqueous humor concentration of IL-1ß was found between patients with POAG and control subjects (0.5±0.8 versus 0.4±0.8 pg/ml; p=0.85.) Concentrations of IL-1α, TNF-α, and FasL were below limits of detection. No significant correlation was found between IL-6 concentration and age, duration of disease, cup/disc ratio, or mean deviation. CONCLUSIONS: In the present study, we found significantly lower concentrations of IL-6 in the aqueous humor of patients with POAG.

Accuracy of matching optic discs with visual fields: the European Structure and Function Assessment Trial (ESAFAT).

PURPOSE: To determine the ability of ophthalmologists across Europe to match stereoscopic optic disc photographs to visual fields of varying severity. DESIGN: Evaluation and comparison of 2 diagnostic tests. PARTICIPANTS: A total of 109 of 260 invited ophthalmologists in 11 European countries. These had participated in the previous European Optic Disc Assessment Trial (EODAT), a trial on glaucoma diagnostic accuracy based on optic discs only. METHODS: Each participant matched stereo optic disc photographs of 40 healthy and 48 glaucomatous eyes to a visual field chosen from 4 options per disc. The 4 presented visual fields included the corresponding one and 3 other visual fields, varying in severity. The matching accuracy and any inaccuracy per disease severity were calculated. Classification accuracy (as glaucomatous or healthy) was compared with EODAT data. Duplicate slides allowed for the assessment of intraobserver agreement. MAIN OUTCOME MEASURES: Accuracy of matching optic discs with their corresponding visual field and of classifying them as healthy or glaucomatous; intraobserver agreement (κ). RESULTS: The overall accuracy of ophthalmologists for correctly matching stereoscopic optic disc photographs to their visual fields was 58.7%. When incorrectly matched, the observers generally overestimated the visual field severity (P<0.001), notably in eyes with early glaucoma. The intraobserver agreement was, on average, moderate (0.52). CONCLUSIONS: European ophthalmologists correctly matched stereoscopic optic disc photographs to their corresponding visual field in only approximately 59% of cases. In most mismatches, the clinicians overestimated the visual field damage.

Role of interleukin 6-174G>C polymorphism in primary open-angle glaucoma.

PURPOSE: In addition to its proinflammatory effects, interleukin (IL)-6 also possesses antiapoptotic properties. Recently, IL-6 has been reported to protect retinal ganglion cells from pressure-induced apoptosis, indicating a possible role in the pathogenesis of primary open-angle glaucoma (POAG). A common polymorphism in the promoter region of IL-6 gene at position -174 characterized by a substitution from G to C has been found to decrease transcription rate of IL-6. The aim of our study was to investigate a hypothesized association between IL-6-174G>C polymorphism and POAG in Caucasian patients. METHODS. The present case-control study comprised 191 unrelated patients with POAG and 191 control subjects, matched for age and sex. Genotyping of the IL-6-174G>C polymorphism was done using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distribution of IL-6-174G>C did not significantly differ between patients with POAG and control subjects (p>0.05). Presence of the IL-6-174C allele was associated with a nonsignificant odds ratio of 0.78 (95% confidence interval 0.46-1.32; p=0.78) for POAG. CONCLUSIONS: Our findings suggest that the functional IL-6-174G>C polymorphism itself is unlikely a major risk factor for POAG.

Changes in intraocular lens surface roughness during cataract surgery assessed by atomic force microscopy.

PURPOSE: To analyze the changes in optic surface roughness before and after injection of various intraocular lens (IOL) models using atomic force microscopy (AFM). SETTINGS: Departments of Ophthalmology, Medical University of Graz, General Hospital Linz and University Hospital Basel; Upper Austria University, School of Applied Health and Social Sciences, Linz, Austria. DESIGN: Experimental study. METHODS: The morphology and surface roughness of 3 hydrophobic acrylic IOLs from different manufacturers were analyzed by AFM in liquid using the tapping mode. First, AFM was performed on IOLs taken from the original package without further manipulation. In a second step, under sterile conditions, an experienced cataract surgeon loaded the IOLs into the appropriate injection system and pushed them through a system resembling an IOL implantation in cataract surgery; this was followed by AFM evaluation. Finally, 3 samples of a preloaded hydrophilic acrylic IOL taken from the original cartridge were compared with 3 samples that were pushed through the implantation system. RESULTS: Comparison of the arithmetic mean, standard deviation, root mean square, and surface skewness of the IOLs before and after injection showed a significant increase in surface roughness (P<.05). CONCLUSIONS: Standard application procedures of IOLs may alter the IOL surface. Increases in the surface roughness of IOLs may influence postoperative posterior capsule opacification. Further studies are necessary to evaluate the interfacial properties of IOLs.

Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.

PURPOSE: The enzyme cholesterol 24S-hydroxylase (Cyp46A1) is responsible for the conversion of cholesterol to its more polar metabolite 24S-hydroxycholesterol, thereby enabling the intracerebral elimination of cholesterol. An intronic single nucleotide polymorphism in the gene CYP46A1 (IVS2 -150 T>C; rs754203) has recently been associated with primary open angle glaucoma (POAG). This association, however, lacks confirmation in other studies. The purpose of the present study was to investigate a hypothesized association between rs754203 and the presence of POAG in a Central European population of Caucasian descent. METHODS: The present institutional study comprised a total of 581 unrelated subjects: 330 patients with POAG, and 251 control subjects. Main outcome measures are genotype distributions and allelic frequencies determined by polymerase chain reaction. RESULTS: No significant differences in either genotype distribution or allelic frequencies were found between patients with POAG and control subjects (p>0.05). The presence of the rs754203 T-allele was associated with a nonsignificant odds ratio of 0.81 (95% CI: 0.63-1.04; p=0.11) for POAG. CONCLUSIONS: Our data suggest that the rs754203 polymorphism itself is unlikely a genetic risk factor for POAG in Caucasian individuals.

Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in open angle glaucomas.

PURPOSE: Matrix metalloproteinases (MMPs) play an essential role in the turnover of the extracellular matrix and cellular behavior. MMP1, MMP2, and MMP9 have previously been implicated in the pathogenesis of primary open angle glaucoma (POAG) and open angle glaucoma secondary to exfoliation syndrome (XFG), respectively. Functional gene polymorphisms of these MMPs such as MMP1 -1607 1G/2G (rs1799750), MMP2 -1306 C/T (rs243865), MMP2 -1575 G/A (rs243866), and MMP9 Q279R (rs17576) are thus plausible candidates as risk factors for open angle glaucomas. The purpose of the present study was to investigate hypothesized associations between these polymorphisms and the presence of POAG and XFG in a Caucasian population. METHODS: The present case-control study included 322 patients with POAG, 202 patients with XFG, and 248 control subjects. Genotyping of polymorphisms was done using polymerase chain reaction. RESULTS: No significant differences in either genotype distributions or allelic frequencies of MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R were found between patients with POAG and control subjects and patients with XFG and control subjects, respectively (p>0.05). The presence of POAG or XFG was not predicted by any of the investigated polymorphisms. CONCLUSIONS: Our data suggest that the MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R polymorphisms themselves are unlikely major risk factors among Caucasian patients with either POAG or XFG.

Clinical assessment of stereoscopic optic disc photographs for glaucoma: the European Optic Disc Assessment Trial.

PURPOSE: To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists. DESIGN: Evaluation of diagnostic test and technology. PARTICIPANTS: A total of 243 of 875 invited ophthalmologists in 11 European countries. METHODS: We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers. MAIN OUTCOME MEASURES: Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa). RESULTS: The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRT's best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on average good (0.7). CONCLUSIONS: In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Positive influence of hyaluronate on cell vitality of human conjunctival cells after alkali injuries.

BACKGROUND: To analyse the influence of hyaluronate (HA) on the cell vitality of human conjunctival cells after chemical injuries from NaOH or alkali-containing household cleaners. METHODS: Human conjunctival cells (Chang cells) were incubated either with NaOH solutions or dilutions of household cleaners. HA (0.025%) was added to the cell culture medium of part of the cells subsequent to chemical injuring. After 24 h the cell vitality of the HA-incubated cells, determined by MTS assay (Cell Titer 96(R) Aqueous One Solution Cell Proliferation Assay), was compared to the control cells without HA addition. RESULTS: The addition of HA to the cell culture medium subsequent to chemical injuring resulted in a significantly lower decrease in cell vitality (mean difference: 11.79; p = 0.00; CI = 98%). CONCLUSION: Because HA attenuates the decrease in cell vitality of alkali-damaged human conjunctival cells, formulations containing HA may be recommended for the treatment of chemical injuries to the anterior part of the eye.

TNF-alpha -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.

PURPOSE: TNF-alpha has been suggested to participate in the pathogenesis of exfoliation glaucoma (XFG). The purpose of the present study was to investigate a hypothesized association between two common functional polymorphisms in the promoter region of the TNF-alpha gene (TNF-alpha -308 G>A, rs1800629, and TNF-alpha -238 G>A, rs361525) and the presence of XFG in a Caucasian population. METHODS: The present case-control study comprised 408 participants (204 patients with XFG and 204 control subjects). Control subjects were matched for age and sex. Genotypes of the TNF-alpha -308 G>A and TNF-alpha -238 G>A polymorphisms were determined by polymerase chain reaction (restriction fragment length polymorphism). RESULTS: No significant differences regarding genotype distribution or allelic frequencies were found between patients and control subjects (p>0.025). The presence of the TNF-alpha -308 G-allele was associated with an insignificant odds ratio of 0.98 (95% confidence interval [CI]: 0.66-1.46; p=0.99) while the presence of the TNF-alpha -238 G-allele was associated with an insignificant odds ratio of 0.64 (95% CI: 0.33-1.23; p=0.25). CONCLUSIONS: Our data suggest that both the TNF-alpha -308 G>A and the TNF-alpha -238 G>A polymorphisms are unlikely to be major risk factors for XFG in an European population of Caucasian descent.

Determination of uric acid concentrations in human tear fluid, aqueous humour and serum.

PURPOSE: The aim of this investigation was to assess and compare levels of uric acid in human tear fluid, aqueous humour and serum in cataract patients in order to obtain information about uric acid-dependent antioxidative status. METHODS: Reflex tear fluid, aqueous humour and serum were obtained from 103 cataract patients (52 women, 51 men). Uric acid was determined by a reversed phase chromatographic method with electrochemical detection. The Randox test was used to measure the contribution of uric acid to the total antioxidative status (TAS) of these body fluids. RESULTS: Mean concentrations of uric acid were 20 +/- 8 microg/ml in tear fluid, 18 +/- 6 microg/ml in aqueous humour and 58 +/- 15 microg/ml in serum. Significantly less uric acid was found in tear fluid (p < 0.01) and aqueous humour (p < 0.01) in female cataract patients compared with male cataract patients. There was a significant positive correlation between uric acid content in tear fluid, aqueous humour and serum, respectively (p < 0.01). The contribution of uric acid to TAS (Randox test) amounted to 38% in tear fluid, 10% in aqueous humour and 37% in serum. CONCLUSIONS: Uric acid was found in comparable amounts in tear fluid and aqueous humour, but these were two- to threefold lower than in serum. Female cataract patients had lower uric acid values in tear fluid and aqueous humour compared with male cataract patients. Uric acid is an important antioxidant, as proven by its contribution to TAS as determined by the Randox test. The precise role of uric acid in the antioxidative reactions in tear fluid and aqueous humour is still under debate.

Plasminogen activator inhibitor-1 4G/5G gene polymorphism and primary open-angle glaucoma.

PURPOSE: Alterations of the plasmin system have been suggested to participate in the multifactorial pathogenesis of primary open-angle glaucoma (POAG). The main physiological inhibitor of the plasmin system is plasminogen activator inhibitor-1 (PAI-1), which leads to decreased degradation of extracellular material. Interestingly, elevated PAI-1 levels in the aqueous humor of patients with POAG have been reported. A common polymorphism within the promoter region (PAI-1 4G/5G) has previously been shown to reduce the gene transcription rate of PAI-1. The purpose of the present study was to investigate a hypothesized association between PAI-1 4G/5G and the presence of POAG in a Caucasian population. METHODS: The present case-control study comprised 212 unrelated patients with POAG and 212 healthy control subjects, matched for age and sex. Genotyping of PAI-1 4G/5G polymorphisms was done using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distributions of PAI-1 4G/5G did not significantly differ between patients with POAG and control subjects (PAI-1 4G/5G: 29.7% versus 29.7%). Presence of the PAI-1 4G-allele was associated with a nonsignificant odds ratio of 0.98 (95% confidence interval: 0.74-1.30) for POAG. CONCLUSIONS: Our data suggest that PAI-1 4G/5G itself is unlikely to be a major risk factor among Caucasian patients with POAG.