Ultrastructural analysis of explanted CyPass microstents and correlation with clinical findings.

PURPOSE: The purpose of this study was to obtain insight into cellular processes after CyPass microstent implantation into the supraciliary space. With this knowledge, we expected to find some reason for surgical failure. METHODS: Nine CyPass microstents of 8 patients with primary open-angle glaucoma (n = 1), pseudoexfoliation glaucoma (n = 5), uveitic glaucoma (n = 1), and posttraumatic open-angle glaucoma (n = 1) were explanted due to recurrence of IOP elevation, corneal decompensation, or persistent hypotony. The explants were processed for light and transmission electron microscopy. RESULTS: Fibrotic material, consisting of collagen fibrils, microfibrils, pseudoexfoliation fibrils produced by activated fibroblasts, was detected in the stent lumen of 4/5 pseudoexfoliation glaucoma patients and also in posttraumatic open-angle glaucoma. Fibrotic material was also present on the outer surface and within fenestrations of the majority of stents. Complete absence of fibrotic reaction was noticed in 3 of 9 microstents. CONCLUSION: Although MIGS is known to be less invasive than conventional surgery, implants placed in the suprachoroidal space may be adversely affected by a fibrotic tissue reaction resulting in implant failure. Understanding mechanisms and risk factors leading to fibrotic scarring following antiglaucomatous surgery may help to develop novel strategies that improve surgical outcome.

Optical coherence tomography in patients with a history of juvenile multiple sclerosis reveals early retinal damage.

BACKGROUND AND PURPOSE: Some 3%-10% of patients with multiple sclerosis (MS) experience disease onset before the age of 18 years ('early' onset MS, EOMS). Optical coherence tomography is a non-invasive method to measure retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) and may be useful to differentiate axonal and neuronal damage in the retina of patients with a history of EOMS. Here RNFLT and TMV in EOMS patients after a mean disease duration of 11.6 years were compared with patients with age- or disease-duration-matched later onset MS (LOMS) and healthy controls (HCs). METHODS: In this observational cross-sectional study at two German academic MS centres, RNFLT and TMV were measured by spectral-domain optical coherence tomography in 32 HCs, 36 EOMS (mean age at onset 15.5 ± 2.0 years) and 58 LOMS patients. RESULTS: In comparison with HCs, EOMS patients displayed a significant reduction of RNFLT and TMV independently of a history of optic neuritis. In particular, RNFLT loss in EOMS was similar to that in LOMS and TMV loss was slightly higher compared with disease-duration-matched LOMS. In a generalized estimating model, the EOMS group also displayed a similar correlation between disease duration and RNFLT or TMV loss to LOMS patients. CONCLUSIONS: These data argue for a significant amount of axonal and neuronal damage in the retina of EOMS patients and may provide a structural basis for the observation that EOMS patients reach states of irreversible disability at a younger age than patients with LOMS.

[Peripheral suprathreshold stimulation in preperimetric glaucoma]. / Uberschwellige periphere Stimulation bei präperimetrischen Glaukomen.

BACKGROUND AND PURPOSE: Early glaucomatous visual field defects can occur outside the central 30 degrees , which is usually examined in perimetric tests used for glaucoma diagnosis and screening. This study aimed to evaluate the diagnostic value of peripheral suprathreshold stimulation in open angle glaucoma before the development of reproducible visual field damage in standard 30 degrees automatic white-on-white perimetry. METHODS: A total of 352 eyes of 352 patients (ages 35-69 years; visual acuity 0.8 or better) from the Erlanger Glaucoma Registry were included in this study. They were divided into two groups: normal eyes and preperimetric glaucoma. All patients underwent a standardized glaucoma examination including Octopus 500EZ static perimetry (G1 program, all three phases); 95 eyes of 95 patients also received a 135-point suprathreshold test pattern of the Humphrey Field Analyzer (model 750i) for detecting peripheral visual field defects. Sensitivity and specificity were calculated for any single test point in phase 3 of the G1 test pattern and the Humphrey 135-point pattern. A score was calculated, and cluster analysis was performed. RESULTS: In 33 of 176 (18.8%) eyes with preperimetric glaucoma, the score was 3 or higher in phase 3 of the G1 program (normal eyes: 19 of 196; 9.7%). For both examination modalities, the highest sensitivity was found in test locations in the superior nasal midperiphery, corresponding to neuroretinal rim loss predominantly in the inferotemporal sector in early glaucomatous optic disc atrophy. CONCLUSION: Positive test results using suprathreshold stimulation in the midperiphery can be found in patients with preperimetric glaucoma at a significantly higher frequency than in normal subjects. Longitudinal studies will show whether such tests can be useful for predicting perimetric manifestation of the disease.

[Flicker provocation with LED full-field stimulation in normals and glaucoma patients]. / Flimmerprovokation im LED-Ganzfeld bei Gesunden und Glaukompatienten.

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.

[Healthy optic discs with large cups--a diagnostic challenge in glaucoma]. / Normale Papillen mit grosser Exkavation -- eine diagnostische Herausforderung bei Glaukomen.

BACKGROUND: Healthy optic discs with large cups are often characterised to be glaucomatous in automated, morphometric analysis. The aim of this study was to investigate the variables of laser scanning tomography (LST) and nerve fibre polarimetry of these disks in comparison to small and normal sized disks. METHODS: 117 eyes (age 49.3 +/- 14.6 years) with healthy, non-atrophic disks (md = 0.8 dB, Tensio 14.3 +/- 2.5 mmHg) of the Erlangen Glaucoma Registry were clinically examined. Morphometry was performed both by planimetry and the HRT I (Heidelberg Engineering, Dossenheim, version 2.01) and with the GDx FCC (Laser Diagnostics, San Diego). 63 eyes initially referred for a large cup were compared to 54 normal eyes. All measurements were analysed globally and in four sectors according to Jonas. RESULTS: The disc area of discs with large cups was significantly larger than that for the normals (3.1 +/- 5.3 vs. 2.2 +/- 4.2 mm (2)). Both the multivariate analysis of the HRT and the GDx revealed a significant correlation with total disk area (R = 0.34, p = 0.0001), with a high percentage of false positive glaucoma eyes among large disks. Cup area and volume showed, in contrast to rim volume and rim area, a significant correlation (R = 0.76, p = 0.0001) with the disc size. Thickness of retinal nerve fibre layer measurements both in HRT and GDx showed higher values for larger disc size with steeper cup measurements. The vertical diameter of the cup increased in comparison to the horizontal to a higher extent with increasing disc size. CONCLUSIONS: By the pronounced enlargement of cup measurements, decreasing nerve fibre thickness values and decreasing ratio of temporal-to-inferior width of the neuroretinal rim, large disks may easily be detected as false glaucomatous by morphometric analysis systems. A better presentation of large discs in a normative database and integration of sectors and disc area in a multivariate analysis may improve the diagnostic abilities of automated morphometric disk analysis.

Automated segmentation of the optic nerve head for diagnosis of glaucoma.

Glaucoma is the second most common cause of blindness worldwide. Low awareness and high costs connected to glaucoma are reasons to improve methods of screening and therapy. A well-established method for diagnosis of glaucoma is the examination of the optic nerve head using scanning-laser-tomography. This system acquires and analyzes the surface topography of the optic nerve head. The analysis that leads to a diagnosis of the disease depends on prior manual outlining of the optic nerve head by an experienced ophthalmologist. Our contribution presents a method for optic nerve head segmentation and its validation. The method is based on morphological operations, Hough transform, and an anchored active contour model. The results were validated by comparing the performance of different classifiers on data from a case-control study with contours of the optic nerve head manually outlined by an experienced ophthalmologist. We achieved the following results with respect to glaucoma diagnosis: linear discriminant analysis with 27.7% estimated error rate for automated segmentation (aut) and 26.8% estimated error rate for manual segmentation (man), classification trees with 25.2% (aut) and 22.0% (man) and bootstrap aggregation with 22.2% (aut) and 13.4% (man). It could thus be shown that our approach is suitable for automated diagnosis and screening of glaucoma.

[Telematic-assisted self-tonometry (TAS)]. / Telematisch assistierte Selbsttonometrie (TAS).

BACKGROUND: Close supervision of intraocular pressure (IOP) means monitoring an important risk factor for glaucoma. METHOD: After instruction in its use, patients measure their own IOP several times a day with the Drager self-tonometer. The measurements are subsequently transmitted to a server via the telephone keypad and recorded separately for each patient. The software enables statistical evaluation of the pressure levels collected. RESULTS: Up to now 30 of 35 patients transmit measurements or had done so for at least 6 months. Registration of measurement levels covering months and years provides the opportunity for optimizing treatment and hence can be considered a start toward quality assurance in the treatment of glaucoma patients. CONCLUSION: TAS is a cost-efficient method for obtaining long-term profiles of eye pressure. Thus, the possibility exists for early therapeutic intervention in patients at risk. The compliance gained by the close relationship between the physician and the patient represents a positive prognostic factor.