Optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy in retinal nerve fiber layer measurements of glaucoma patients.

PURPOSE: To determine the correlations and strength of association between different imaging systems in analyzing the retinal nerve fiber layer (RNFL) of glaucoma patients: optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO). MATERIALS AND METHODOLOGY: 114 eyes of patients with moderate open angle glaucoma underwent spectral domain OCT (Topcon SD-OCT 2000 and Zeiss Cirrus HD-OCT), SLP (GDx VCC and GDx Pro) and CSLO (Heidelberg Retina Tomograph, HRT 3). Correlation coefficients were calculated between the structural parameters yielded by these examinations. The quantitative relationship between the measured RNFL thickness globally and for the four regions (superior, inferior, nasal, temporal) were evaluated with different regression models for all used imaging systems. RESULTS: The strongest correlation of RNFL measurements was found between devices using the same technology like GDx VCC and GDx Pro as well as Topcon OCT and Cirrus OCT. In glaucoma patients, the strongest associations (R²) were found between RNFL measurements of the two optical coherence tomography devices Topcon OCT and Cirrus OCT (R² = 0.513) and between GDx VCC and GDx Pro (R² = 0.451). The results of the OCTs and GDX Pro also had a strong quantitative relationship (Topcon OCT R² = 0.339 and Cirrus OCT R² = 0.347). GDx VCC and the OCTs showed a mild to moderate association (Topcon OCT R² = 0.207 and Cirrus OCT R² = 0.258). The confocal scanning laser ophthalmoscopy (HRT 3) had the lowest association to all other devices (Topcon OCT R² = 0.254, Cirrus OCT R² = 0.158, GDx Pro R² = 0.086 and GDx VCC R² = 0.1). CONCLUSION: The measurements of the RNFL in glaucoma patients reveal a high correlation of OCT and GDx devices because OCTs can measure all major retinal layers and SLP can detect nerve fibers allowing a comparison between the results of this devices. However, CSLO by means of HRT topography can only measure height values of the retinal surface but it cannot distinguish between different retinal layers. This may explain the rather poor correlations and associations between CSLO measurements and those of all other imaging devices which makes it difficult to compare HRT 3 nerve fiber data. These correlations are important in clinical routine especially when different techniques are used in the follow-up of glaucoma patients.

Trabeculectomy Improves Vessel Response Measured by Dynamic Vessel Analysis (DVA) in Glaucoma Patients.

PURPOSE: To determine the effects of surgical IOP reduction (trabeculectomy) on retinal blood flow parameters in glaucoma patients using Dynamic Vessel Analysis (DVA). METHODS: 26 eyes of 26 patients with progressive primary open-angle glaucoma (POAG) despite maximal topical therapy were examined before and after trabeculectomy. The responses of the retinal vessels to flickering light provocation were measured with DVA the day before surgery and 4 to 6 weeks after trabeculectomy. Between 3 and 4 weeks before surgery all local therapies were stopped and a systemic therapy with acetazolamide and conservative free topic steroidal eye drops was started. RESULTS: In 19 patients (73%), an inadequate response to the flicker stimulation was measured preoperatively. In these patients, the maximum dilation of arteries and veins was reduced significantly as compared to healthy eyes. In this group, the maximum dilation of the arteries following the flicker provocation improved from 1.4% before to 3.8% following trabeculectomy (p<0.01). In retinal veins, this parameter increased from 3.1% to 4.6% (p<0.05). In the 7 patients whose arterial and venous reactions to flickering light provocation preoperatively did not differ from healthy eyes, there was no significant change after surgery. The initial baseline values of arteries and veins (MU) did not deviate significantly in both groups. CONCLUSION: POAG patients with progressive disease and impaired vascular regulation profit from IOP lowering trabeculectomy concerning vascular reactivity and dilative reserve, indicating a possible improvement of retinal perfusion following effective IOP control. Future studies with long-term follow-up must determine the clinical importance of these findings for the treatment of glaucoma patients.

Laser cyclophotocoagulation enhances the regulative capacity of retinal vessels in glaucoma.

PURPOSE: To determine the effects of laser surgical IOP reduction by means of transscleral cyclophotocoagulation (CPC) on retinal blood flow parameters in glaucoma patients using Dynamic Vessel Analysis (DVA). MATERIALS AND METHODOLOGY: 26 patients (average age: 70 years) with a long history of primary open angle glaucoma underwent CPC. The effect on the reactive capacity of retinal vessels was assessed before and 6-8 weeks after CPC by means of the Dynamic Vessel Analyzer (DVA) using flicker light provocation. RESULTS: In our group of POAG patients, IOP was significantly reduced about approximately 20% by CPC while systemic blood pressure and heart rate were not changed. The most obvious differences between the pre- and postoperative DVA measurements could be observed in the maximal dilation of the retinal arteries which increased from 0.75 % (+/- 0.6) to 3.17 % (+/- 0.5) with an average increase of 2.4 % (p<0.01). In addition, the ability of the arteries for constriction improved significantly (p<0.05) while the dynamic responses of the veins and the initial baseline values (MU) of the vessel diameters did not change. CONCLUSIONS: Our results of DVA measurements after an IOP-lowering laser surgical intervention (CPC) reveal a significant recovery of the regulative capacity of retinal arteries in glaucoma patients that has up to now neither been properly documented nor appreciated. Future studies with long-term follow-up must determine the clinical importance of these findings for the treatment of glaucoma patients.

Transpalpebral electrotherapy for dry age-related macular degeneration (AMD): an exploratory trial.

PURPOSE: To evaluate the effect of transpalpebral electrotherapy on patients with dry age-related macular degeneration (AMD). METHODS: 22 patients were randomized in two groups to either receive therapy (n = 12) or placebo (n = 10). There was no statistically significant difference for age and initial visual acuity (VA) between the two groups (p = 0.6; ANOVA). Treatment was performed on 5 consecutive days. On each day two sessions were applied. Every session included 8 spots (40 sec/spot) around the eye globe. The current applied (changing frequency 5-80 Hz) varied individually between 150 and 220 µA. Patients were examined before treatment, at the end of the 5-day treatment period, after 4 weeks and at 6 months. Examinations included a standardized VA testing, using ETDRS letters, contrast sensitivity, macular sensitivity and fixation stability using microperimetry and measurements with SD-OCT. RESULTS: At the end of week 1, mean VA improved markedly (p = 0.001; T test), with 7 out of 12 patients showing an improvement of more than 5 letters. After 4 weeks, there was an improvement of more than 10 letters in 3 patients (mean + 5.7 letters; p = 0.001; T test) whereas at 6 months a loss of 1.6 letters was observed. Only 4 (33%) of our patients did not show any improvement at all. Contrast sensitivity displayed a similar pattern. Within one week after treatment, there was a rapid improvement (+4.4 optotypes; p = 0.006; T test). After 6 months, contrast sensitivity declined again (+1.5 optotypes; p = 0.2; T test). Compared to the placebo group changes on VA failed statistical significance (p = 0.1 at 4 week; T test) whereas changes on contrast sensitivity were statistically significant (p = 0.01 at week 4; T test). No adverse events were seen or reported during the study period. CONCLUSIONS: To the best of our knowledge, this is the first report of a transpalpebral electrostimulation in patients with dry AMD that demonstrates a temporary increase in visual function in some of these patients; results that seem to justify further research on this potential treatment option for dry AMD.

Comparison of Spectralis-OCT, GDxVCC and GDxECC in assessing retinal nerve fiber layer (RNFL) in glaucomatous patients.

BACKGROUND: Glaucomatous optic neuropathy is characterized by a progressive loss of retinal ganglion cells (RGCs). The defects in the peripapillary retinal nerve fiber layer (RNFL) have been reported to be the earliest sign of glaucoma. We determined the agreement between RNFL thickness assessments from spectral-domain OCT (Spectarlis HRA + OCT; Heidelberg Engeneering, Heidelberg, Germany), scanning laser polarimetry (SLP) with variable cornea compensation (GDxVCC; Carl Zeiss Meditec, Dublin, CA, USA), and SLP with enhanced cornea compensation (GDxECC; Carl Zeiss Meditec, Dublin, CA, USA) in glaucomatous patients. Furthermore, we investigate the influence of typical scan score (TSS) on the results of GDx assessments. METHODS: The enrolled subjects were devided into different groups by modified HODAPP visual field criteria. The peripapillary RNFL thickness was assessed with the three devices . ANOVA test, Pearson and Spearman correlation coefficient, and Bland-Altman plots were used to analyse the RNFL thickness assessments. RESULTS: Ninety-two eyes from 92 glaucomatous subjects were analysed. These were divided into four groups: preperimetric glaucoma (n = 26), mild glaucoma (n = 18), moderate glaucoma (n = 21), and severe glaucoma (n = 27). For Spectralis-OCT, the average RNFL thickness (mean ± SD) was 99.25 ± 26.31 µm, 80.52 ± 16.63 µm, 71.59 ± 21.15 µm, and 63.85 ± 20.86 µm for preperimetric, mild, moderate, and severe glaucoma respectively. For GDxVCC, the corresponding assessments were 52.63 ± 8.18 µm, 52.95 ± 10.20 µm, 46.77 ± 10.62 µm, and 49.70 ± 13.34 µm. For GDxECC, the assessments were 49.35 ± 6.52 µm, 45.92 ± 7.21 µm, 42.19 ± 8.00 µm, and 39.53 ± 8.45 µm. All Spectralis-GDxVCC and Spectralis-GDxECC differences were statistically significant by ANOVA test. The differences between GDxVCC and GDxECC were statistically significant only for severe glaucoma. There was a highly significant correlation between Spectralis-OCT and GDxECC, as well as Spectralis-OCT and GDxVCC, in assessing the RNFL thickness. The best instrument agreement was found between GDxECC and Spectralis-OCT. The RNFL thickness assessed with Spectralis-OCT and GDxECC showed a better correlation to visual field defects than GDxVCC. Evaluating GDx assessments with typical retardation pattern GDxVCC and GDxECC showed very similar RNFL thickness results. CONCLUSIONS: RNFL thickness assessments between GDxVCC, GDxECC, and Spectralis-OCT cannot be directly compared. The assessments are generally higher with Spectralis-OCT than with GDxVCC and GDxECC, because of differences in method of the devices. The atypical retardation pattern has a major impact on the RNFL thickness results of GDx devices. This must be taken into account when evaluating the assessed RNFL thickness results.

Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.

PURPOSE: To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). MATERIALS AND METHODOLOGY: A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. RESULTS: Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. CONCLUSIONS: While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.

Comparison of the Colvard, Procyon, and Neuroptics pupillometers for measuring pupil diameter under low ambient illumination.

PURPOSE: To compare three different pupillometers (Colvard, Procyon, and Neuroptics) for determining pupil diameter at 0.04 and 0.4 lux ambient illumination. METHODS: In 92 eyes of 46 healthy volunteers, pupil diameter was measured at 0.04 and 0.4 lux. After dark adaptation for 2 minutes, measurements were performed with each device by two examiners. Interobserver agreement, instrument agreement, and repeatability were analyzed. RESULTS: Mean pupil diameter was 6.63+/-0.68 mm, 6.24+/-1.01 mm, and 6.99+/-0.67 mm at 0.04 lux and 6.22+/-0.74, 4.64+/-1.04, and 6.73+/-0.72 mm at 0.4 lux with the Colvard, Procyon, and Neuroptics pupillometers, respectively. The interobserver disagreement ranged within narrower limits for the Colvard (0.04 lux: -1.0 to 0.5 mm; 0.4 lux: -0.75 to 1.0 mm) and Neuroptics (0.04 lux: -1.0 to 0.5 mm; 0.4 lux: -1.7 to 0.7 mm) than for the Procyon (0.04 lux: -0.74 to 1.14 mm; 0.4 lux -1.82 to 2.4 mm) under both light conditions. Instrument agreement ranged within narrower limits for the Colvard versus Neuroptics (0.04 lux: -1.3 to 0.75 mm; 0.4 lux: -1.55 to 1.40 mm) than for the Neuroptics versus Procyon (0.04 lux: -1.06 to 2.69 mm; 0.4 lux: 0.18 to 3.69 mm) or Colvard versus Procyon (0.04 lux: -0.63 to 2.60 mm; 0.4 lux: -0.32 to 3.13 mm) at both light levels. At 0.04 lux, repeatability showed no measurement difference outside +/-0.5 mm for the Colvard and Neuroptics; for the Procyon, 25% of consecutive measurements showed a difference >+/-0.5 mm. At 0.4 lux, 2.5% of consecutive measurements for the Colvard and 5% for the Neuroptics differed by >+/-0.5 mm; for the Procyon, 13% of measurements differed by more than this amount. CONCLUSIONS: Pupil diameters under both light conditions were largest with the Neuroptics pupillometer and smallest with the Procyon. The most "examiner independent" Procyon pupillometer performed poorly. The underestimation of the pupil diameter might have severe consequences for refractive surgery patients. The Neuroptics pupillometer showed a high interobserver agreement and repeatability and therefore high safety.

Episcleral venous pressure in untreated primary open-angle and normal-tension glaucoma.

The aim of this prospective study was to investigate episcleral venous pressure (EVP) in different forms of glaucoma in comparison with age-matched controls. EVP was measured by means of a venomanometer in 32 eyes with untreated primary open-angle glaucoma (POAG), 36 eyes with untreated normal-tension glaucoma (NTG) as well as 56 control eyes without ophthalmological disease other than cataract. In addition to ophthalmological standard examination, cardiovascular parameters such as systolic and diastolic blood pressure and heart rate were recorded. In the POAG group, EVP was 12.1 +/-0.5 mm Hg and in the NTG group 11.6 +/- 0.4 mm Hg. This was significantly different from EVP of the controls (9.5 +/- 0.2 mm Hg). The EVP/intraocular pressure (IOP) ratio was significantly different in NTG patients (80.0% +/- 3.2) in comparison with both POAG patients (67.1% +/- 2.8) and controls (69.2% +/- 2.4). The difference between IOP and EVP (IOP - EVP) was 6.2 +/- 0.6 in the POAG, 3.1 +/- 0.45 in the NTG and 4.5 +/- 0.4 in the control group. All these values were significantly different from each other. Regression analysis revealed a significant linear correlation between EVP and IOP in both the NTG and the POAG group. In the control group, however, the correlation was weak. This study is the first to demonstrate differences in EVP between untreated NTG and POAG and an age-matched healthy control group.

Substance P and opioid peptidergic innervation of the anterior eye segment of the rat: an immunohistochemical study.

Recently discovered endogenous opioid peptides such as nociceptin are known to modulate neurotransmitter release of primary afferent neurons (especially substance P, SP) and they have also been demonstrated in peripheral nerve fibres. The aim of this study was to investigate the opioid peptidergic innervation of the anterior eye segment and to compare it with the innervation pattern of SP in order to shed light on the functional relationship between these peptides. Anterior eye segments of 20 rat eyes were cut in a tangential plane and the sections stained with antibodies against SP, nociceptin, nocistatin, endomorphin 1 and 2, leu-enkephalin and met-enkephalin. Sections of the spinal cord or brain were used as positive controls. Numerous SP-immunoreactive nerve fibres were found in the conjunctiva, cornea, episclera, trabecular meshwork, iris and ciliary body. A weak staining for met-enkephalin and leu-enkephalin could only be found in the iris and anteriormost ciliary body. Nerve fibres immunoreactive for nociceptin, nocistatin, and endomorphin 1 or 2 could not be detected in any part of the anterior eye segment. It is tempting to speculate that the opioid peptidergic innervation of the anterior ciliary body may play a role in the modulation of intraocular inflammation.

Antiphospholipid antibodies in patients with sensorineural hearing loss.

Sensorineural hearing loss can be associated with autoimmune diseases and the presence of antiphospholipid antibodies. Sixty patients (mean age 47 years, range 18-76 years) with sudden sensorineural hearing loss were studied with audiograms, stapedial thresholds, otoacoustic emissions, positional and caloric testing. The serologic testing included antibodies against phosphatidylserine and beta(2)-glycoprotein. Additionally, a group of 34 patients (mean age 65 years, range 31-81 years) with normal tension glaucoma was examined because in a previous study these patients were reported to have elevated concentrations of antiphospholipid antibodies with a coincidence of progressive sensorineural hearing loss. The baseline for antiphospholipid antibody levels was established in a control group of 40 healthy blood donors. In 12 of the 60 patients with sudden sensorineural hearing loss, levels of antiphospholipid antibodies were elevated. Antiphosphatidylserine IgM antibodies were significantly lower compared to controls and patients with the combination of hearing loss and normal tension glaucoma (Fisher's exact two-sided test, P < 0.01). Our data suggest that antibodies against beta2-glycoprotein seem to coincidence with an acute event, such as sudden sensorineural hearing loss, whereas antibodies against phosphatidylserine IgG are detectable in the prolonged sequel, such as in patients with progressive sensorineural hearing loss and normal tension glaucoma.

Scanning laser polarimetry in myopic and hyperopic subjects.

PURPOSE: To investigate the effect of refraction error and axial length on retinal nerve fiber layer (RNFL) measurements as obtained by scanning laser polarimetry (SLP). METHODS: Besides ophthalmological standard examination (refractive error, keratometry, visual acuity, slit-lamp examination, applanation tonometry, funduscopy), perimetry, axial length measurement by means of ultrasound, and SLP were performed. Seventy-five myopic eyes (between -0.75 D and -8.5 D), 24 hyperopic eyes (0.75 D-6.5 D) and 40 emmetropic eyes were investigated. SLP parameters were compared in the different groups. RESULTS: The statistical analysis of the absolute thickness values of SLP revealed highly significant ( P< 0.01) reductions in average thickness, ellipse average, superior average, inferior average, and superior integral in both myopic and hyperopic eyes in comparison with the emmetropic control eyes. The amount of reduction was between 12.9% (inferior average; myopia) and 30.2% (superior integral; hyperopia). There were no significant differences between myopes and hyperopes. A significant linear correlation for many of the SLP parameters with the refractive error (spherical equivalent) but not with axial length was found in both the hyperopic and the myopic group. CONCLUSIONS: Despite a wide interindividual range, SLP measurement values decrease with increasing myopia and hyperopia. In clinical practice, such reduced RNFL thickness values should be viewed with the necessary caution and additional polarimetric signs for glaucomatous damage should be taken into consideration.

Influence of cataract surgery with implantation of different intraocular lenses on scanning laser tomography and polarimetry.

PURPOSE: To describe the influence of cataract surgery with implantation of different intraocular lenses on scanning laser tomography (SLT) and scanning laser polarimetry (SLP) and to measure the birefringent properties of intraocular lenses in a laboratory setting. DESIGN: Prospective cohort study. METHODS: The influence of phacoemulsification cataract surgery with intraocular lens implantation (56 polymethylmethacrylate [PMMA; 31 Pharmacia/Upjohn 811 B and 25 Domilens Flex 60]; 25 hydroxyethylmethacrylate/methylmethacrylate (HEMA/MMA) [Technomed, Memory Lens]; 32 silicone [Allergan Si40]; 25 acrylic [Storz Hydroview]) on SLP and SLT measurements was evaluated preoperatively and 3 to 4 weeks postoperatively in 138 eyes of otherwise healthy patients. Lens opacities were classified according to the Lens Opacities Classification System III (LOCS III). Imaging was performed with TopSS and GDx (Laser Diagnostic Technologies, San Diego, California, USA) for SLT and SLP, respectively. Additionally, birefringent properties of intraocular lenses were measured in a laboratory setting. RESULTS: Our results show that imaging with SLT and SLP is possible with lens opacity-induced visual acuity reductions down to 0.2 and 0.16, respectively. There were no significant differences in the topographic parameters assessed before and after cataract surgery with SLT. However, standard deviations between three within-session single measurements were smaller postoperatively. Nerve fiber layer patterns were similar before and after cataract surgery with SLP, whereas certain total nerve fiber layer thickness values were significantly higher postoperatively. As a consequence, "the number" is significantly lower in the Domilens Flex 60 group (P =.01) and in the Storz Hydroview group (P =.02), and with a tendency also in the other groups as well. Measurements with a high-resolution optical bench revealed no birefringent properties of the implanted lenses. CONCLUSIONS: Our results indicate that after cataract surgery with intraocular lens implantation some SLP values are altered significantly, whereas SLT parameters are not influenced. These findings are of clinical interest, especially in the follow-up of glaucoma patients.

[Ligneous conjunctivitis in a patient with plasminogen type I deficiency--case report with review of literature]. / Conjunctivitis lignosa bei Typ-I-Plasminogenmangel - Kasuistik mit Literaturübersicht.

BACKGROUND: Ligneous conjunctivitis is a rare chronic pseudomembranous conjunctivitis. It forms nodular masses on the palpebral conjunctiva. Beside the conjunctival affection pseudomembranes can also be found on other mucosal tissues. PATIENT: We report on a male baby who had a ventriculoperitoneal shunt due to hydrocephalus internus on his fourth day after birth. Recurrent pseudomebranous conjunctivitis started in the first week of life. This was refractory to drug therapy and reoccurred soon after surgical procedure. The analysis of clotting parameters revealed homozygous plasminogen deficiency. CONCLUSION: Recently type I plasminogen deficiency seems to be a major reason for developing conjunctivitis lignosa. Homozygous and heterozygous mutations in the plasminogen gene are found. At the moment no satisfactory therapy is available. Cases with mild ophthalmological symptoms seem to be positively influenced by a therapy of topical steroids combined with heparin. In severe cases with generalised symptoms systemic therapy with lys-plasminogen is necessary. High costs and poor bioavailability complicate systemic therapy. Improved plasminogen variants for treatment of severe type I plasminogen deficiency would be of great clinical importance.