Biomedical subjects

Norbert Pfeiffer

Publications and source records attributed to Norbert Pfeiffer.

At least 19 recordsLinked to original sources

PubMed2026

A Comprehensive Assessment of the Shared Genetic Architecture between Myopia and Open-Angle Glaucoma.

OBJECTIVE: Individuals with high myopia have an increased prevalence of open-angle glaucoma (OAG). We aim to clarify the possibly shared genetic architecture of myopia and OAG, in particular in high myopes with myopic macular degeneration (MMD), where OAG screening is highly challenging. DESIGN: Individual participant data meta-analysis of one-sample Mendelian randomization analyses and pleiotropic analysis under a composite null hypothesis. PARTICIPANTS: A total of 34 825 participants from 6 population-based cohort studies and 1 high myopia case-control study, including 708 OAG and 1953 high-myopia cases. METHODS: First, we calculated and validated genetic risk scores (GRSs) for OAG and myopia in each cohort. We subsequently meta-analyzed linear and logistic regression models for the association of a myopia GRS with OAG, intraocular pressure (IOP), and vertical cup-to-disc ratio (VCDR), and the association of an OAG-GRS with high myopia, axial length, and spherical equivalent. We stratified the analysis of OAG in different stages of axial elongation, and in high myopes with or without MMD. Pleiotropic analysis under a composite null hypothesis was applied to genome-wide association study summary statistics. MAIN OUTCOME MEASURES: Odds ratio (OR) of OAG and high myopia, and mean difference in IOP, VCDR, axial length, and spherical equivalent. RESULTS: One standard deviation (SD) increase in myopia GRS was associated with an OR (95% CI) of 1.18 (1.09, 1.28) for OAG, a beta (95% CI) of 0.04 (0.00, 0.08) mmHg in IOP, and of 0.005 (0.003, 0.007) in VCDR. The OAG-GRS was not significantly associated with high myopia compared to emmetropes, but a 1 SD increase was associated with a beta (95% CI) of 0.05 (0.01, 0.08) mm in axial length and of -0.05 (-0.10, -0.00) diopters in spherical equivalent. One SD increase in OAG-GRS had a substantially larger effect on OAG in high myopes with MMD, with an OR (95% CI) of 3.83 (1.89, 7.78) compared to 1.55 (1.24, 1.94) in emmetropes. Finally, we identified 95 independent pleiotropic single-nucleotide polymorphisms (SNPs). CONCLUSIONS: There is strong evidence for pleiotropy between myopia and OAG. Further research into the biological mechanisms of the identified pleiotropic SNPs is needed. An OAG-GRS might help to clinically estimate OAG risk, in particular in individuals with MMD. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Axial length↗

PubMed2006

Central corneal thickness in the European Glaucoma Prevention Study.

PURPOSE: To measure central corneal thickness (CCT) within the participants of the European Glaucoma Prevention Study (EGPS). This study was designed to test if lowering intraocular pressure (IOP) by means of dorzolamide is able to prevent or delay conversion from ocular hypertension to glaucoma. DESIGN: Randomized, double-masked, controlled, observational clinical trial. PARTICIPANTS: Eight hundred fifty-four of 1077 ocular hypertensive participants within the EGPS were investigated. Four hundred twenty-nine patients were treated with dorzolamide and 425 patients received placebo. INTERVENTION: Treatment with dorzolamide or placebo (the vehicle of dorzolamide) in 1 or both eyes. MAIN OUTCOME MEASURES: Central corneal thickness as measured by ultrasound pachymetry (DGH-500 Pachette; DGH Technologies, Exton, PA). The CCT measurements were obtained in the morning before measuring IOP. Five measurements were taken from each eye of each patient within 5 minutes of application of anesthetic eye drops. RESULTS: Mean CCT was 572.6+/-37.4 microm (range, 458.5-695.6 microm). The CCT was higher in younger patients, male patients, and diabetic patients. Mean CCTs for the 429 patients receiving dorzolamide were 574.2+/-38.48 microm (range, 458.5-695.6 microm) and 571.0+/-36.21 microm (469.7-690.1 microm) for the 425 patients receiving placebo (P = 0.205). Central corneal thickness did not correlate with refraction, baseline IOP, or systemic hypertension. CONCLUSION: Central corneal thickness measurements within the EGPS were greater than those reported in other studies of normal eyes without ocular hypertension. Larger CCT measurements correlated with male gender, younger age, and diabetes.

Adult↗

PubMed2006

Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study.

OBJECTIVE: To evaluate the predictive factors of open-angle glaucoma (OAG) in patients affected by ocular hypertension enrolled in the European Glaucoma Prevention Study (EGPS). DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: One thousand seventy-seven patients, > or =30 years old, were enrolled at 18 European centers. The patients met inclusion criteria: intraocular pressure, 22 to 29 mmHg; 2 normal and reliable visual fields (VFs) (on the basis of mean deviation and corrected pattern standard deviation [PSD]); and a normal optic disc, as determined by an optic disc reading center. INTERVENTION: Treatment with dorzolamide or a placebo (the vehicle of dorzolamide) in one or both eyes. MAIN OUTCOME MEASURES: Efficacy end points were VF and/or optic disc changes. Baseline demographic and clinical data were collected before randomization, except for corneal thickness measurements, which were determined during follow-up. Proportional hazards models were used to identify factors that predicted which participants in the EGPS had developed OAG. RESULTS: In multivariate analyses, factors that predicted the development of OAG included older age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.04-1.69), larger vertical cup-to-disc (C/D) ratio (HR, 1.34; 95% CI, 1.14-1.58), larger vertical C/D ratio asymmetry (HR, 1.46; 95% CI, 1.11-1.93), higher PSD (HR, 1.66; 95% CI, 1.15-2.38), and lesser central corneal thickness (HR, 1.32; 95% CI, 1.05-1.67). CONCLUSIONS: Baseline age, vertical C/D ratio, vertical C/D ratio asymmetry, and PSD were good predictors of the onset of OAG in the EGPS. Central corneal thickness was found to be a powerful predictor of the development of OAG. The EGPS results agree with the findings of the Ocular Hypertension Treatment Study and support the need for a thorough evaluation of patients with ocular hypertension.

Antihypertensive Agents↗

PubMed2006

Analysis of IgG antibody patterns against retinal antigens and antibodies to alpha-crystallin, GFAP, and alpha-enolase in sera of patients with "wet" age-related macular degeneration.

BACKGROUND: The aim of this study was to compare the IgG antibody patterns against retinal antigens in sera of patients with age-related macular degeneration (AMD) and healthy subjects to learn more about possible immunological aspects of this disease and to identify some of the most important antigens. METHODS: Sera of 140 patients were analyzed: healthy volunteers (CO, n=101) and patients with "wet" age-related macular degeneration (AMD, n=39). The sera were tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques and some antigens were identified via LC-MS/MS. RESULTS: All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistical significant difference between the antibody profiles of the AMD and the CO group (P=0.000023). Not only up-regulations of antigen-antibody-reactivities in the AMD group at some molecular weight ranges, e.g. at 46 and 52 kDa, could be seen, but also down-regulations, e.g. at 18 and 36 kDa. The 18 kDa antigen band was identified as alphaB-crystallin, the band at 46 kDa as alpha-enolase, and one at 52 kDa as glial fibrillary acidic protein. CONCLUSIONS: We could demonstrate that both groups (wet AMD and CO) show complex IgG antibody patterns against retinal antigens, which are highly specific for each group. This provides further hints for the immunological basis of the disease. These changes in the antibody profiles in "wet" AMD could represent a secondary response to retinal damage or can play a causative role in the disease.

Adult↗

PubMed2006

Comparison of dynamic contour tonometry and goldmann applanation tonometry in glaucoma patients and healthy subjects.

PURPOSE: To investigate the agreement in the measurement of intraocular pressure (IOP) obtained by dynamic contour tonometry PASCAL (DCT-PASCAL) and Goldmann applanation tonometry (GAT) in glaucoma eyes and healthy eyes with different central corneal thickness (CCT). DESIGN: Prospective cross-sectional study. METHODS: In a randomized order, three consecutive IOP measurements were performed on 197 eyes of 107 subjects by one examiner using both DCT-PASCAL and GAT on all eyes. Furthermore, ultrasonic pachymetry was performed. The Spearman correlation coefficient (r) was determined to compare IOP readings between DCT-PASCAL and GAT. Regression-based Bland and Altman analysis was used to evaluate agreement between the instruments. RESULTS: Mean IOP values obtained by both instruments were significantly correlated in healthy and glaucoma eyes (all healthy eyes [n = 66]: r = 0.8, P < .001, all glaucoma eyes [n = 131]: r = 0.96, P < .001). Neither GAT nor DCT-PASCAL showed a significant correlation with CCT (GAT: all eyes: r = 0.009, P = .9, DCT-PASCAL: all eyes: r = -0.05, P = .5). Bland and Altman analysis revealed the existence of proportional bias. Thus, 95% limits of agreement between the instruments varied with the actual IOP measurement. CONCLUSIONS: DCT-PASCAL and GAT revealed a strong correlation in IOP measurements between glaucoma and healthy eyes. However, the analysis of agreement indicated some discrepancies between the instruments. Measurements with both GAT and DCT-PASCAL were not correlated with central corneal thickness.

Adult↗

PubMed2006

Effect of a closed foldable equator ring on capsular bag shrinkage in cataract surgery.

PURPOSE: To evaluate the effect of a closed foldable equator ring (CFER) versus a conventional capsular tension ring (CTR) on capsular bag shrinkage. SETTING: Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. METHODS: In this prospective study, 70 eyes of 70 patients were randomized to 2 groups using a 1:1 block scheme. After uneventful cataract surgery, a capsular measuring ring was implanted in all eyes to measure the capsular bag diameter in vivo. In Group 1, a CTR was implanted in the capsular bag. In Group 2, a CFER was inserted. Biometric characteristics such as axial length and the horizontal and vertical corneal radii were measured preoperatively. The capsular bag diameter and capsulorhexis diameter were measured intraoperatively and 2 or 3 days as well as 1 and 3 months postoperatively. RESULTS: There were no statistically significant or clinically relevant between-group differences in covariants such as axial length, vertical and horizontal corneal radii, and capsulorhexis diameter. Eyes with the CTR had slight but statistically significant capsular bag shrinkage from a median of 10.4 to a median of 10.2 mm after 3 months (P<.001). Eyes with the CFER also had slight but statistically significant capsular bag shrinkage from a median of 10.3 to a median of 10.2 mm 3 months postoperatively (P = .021). At baseline, the CTR group had a larger capsular bag diameter, but there were no statistically significant differences between the groups at the 3-month follow-up (P = .669). CONCLUSIONS: No clinically relevant capsular bag shrinkage was observed after implantation of a CFER or a CTR. The expected capsular bag shrinkage was the same in both groups.

Aged↗

PubMed2006

Endothelin antagonism: effects of FP receptor agonists prostaglandin F2alpha and fluprostenol on trabecular meshwork contractility.

PURPOSE: This study analyzes additional mechanisms behind the ocular hypotensive effect of prostaglandin F (PGF) receptor (FP receptor) agonists PGF2alpha and fluprostenol (fluprostenol-isopropyl ester [travoprost]), which reduce intraocular pressure (IOP) in patients with glaucoma probably by enhancing uveoscleral flow. The trabecular meshwork (TM) is actively involved in IOP regulation through contractile mechanisms. Contractility of TM is induced by endothelin (ET)-1, a possible pathogenic factor in glaucoma. The involvement of FP receptor agonists in the ET-1 effects on TM function was studied. METHODS: The effects of FP receptor agonists on contractility of bovine TM (BTM) were investigated using a force-length transducer. The effects of PGF2alpha on intracellular Ca2+ ([Ca2+]i) mobilization in cultured cells were measured using fura-2AM. The expression of the FP receptor protein was examined using Western blot analysis. RESULTS: The ET-1-induced (10(-8) M) contraction in isolated BTM was inhibited by PGF2alpha (10(-6) M) and fluprostenol (10(-6) M). This effect was blocked by FP receptor antagonists. Carbachol-induced contraction or baseline tension was not affected by PGF2alpha or fluprostenol. In cultured TM cells, ET-1 caused a transient increase in [Ca2+]i that was reduced by PGF2alpha. No reduction occurred in the presence of the FP receptor antagonist Al-8810. Western blot analysis revealed the expression of the FP receptor in native and cultured TM. CONCLUSIONS: FP receptor agonists operate by direct interaction with ET-1-induced contractility of TM. This effect is mediated by the FP receptor. Thus, FP receptor agonists may decrease IOP by enhancing aqueous humor outflow through the TM by inhibiting ET-1-dependent mechanisms.

Animals↗

PubMed2006

Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States.

PURPOSE: Glaucoma is characterized by a progressive loss of retinal ganglion cells that results in a characteristic optic neuropathy associated with visual field loss. In previous studies, changes in the antibody profiles have been shown in the sera of patients with glaucoma, and these findings suggest a role for autoimmune involvement in the pathogenesis of glaucoma in some patients. The purpose of this study was to compare the antibody profiles against optic nerve antigens in patients with glaucoma in two different study populations from Germany and the United States. METHODS: One hundred twenty patients were included in the study, 60 from Germany and 60 from the United States: a control group (CTRL, n = 20), a group of patients with primary open-angle glaucoma (POAG, n = 20), and one group of patients with normal-pressure glaucoma (NPG, n = 20) from each country. Western blot analyses against bovine optic nerve antigens were used to detect the IgG antibody patterns present in the patients' sera. The complex antibody profiles were analyzed by multivariate statistical techniques. RESULTS: Complex IgG autoantibody repertoires were present in all patients with glaucoma as well as healthy subjects from both the German and the United States study population. A large similarity between all antibody profiles in both study populations was demonstrated in the number and frequency of both up- and downregulation of antibody reactivities in patients with glaucoma of both national cohorts. The multivariate analysis of discriminance found a significant difference between the glaucoma groups and healthy subjects against optic nerve antigens. As in previous studies, the NPG group revealed the highest variance from the control group (P < 0.01). Furthermore, a newly described antibody biomarker in both study populations was identified as alpha-fodrin. Western blot results revealed that there was an increased frequency and enhanced immunoreactivity to alpha-fodrin (120 kDa) in the sera of patients with NPG. The presence of alpha-fodrin autoantibodies were confirmed by ELISA, in which a highly elevated anti-alpha-fodrin titer in patients with NPG was found to be significantly greater than in the control subjects (P < 0.01) or age-matched patients with POAG (P < 0.04). CONCLUSIONS: Complex IgG antibody patterns against optic nerve antigens can be reproducibly identified in the serum of study populations from the United States and Germany. In both cohorts, patients with glaucoma have characteristic differences in serum autoantibody repertoires from those in control subjects. A newly described autoantibody to alpha-fodrin found in other neurodegenerative diseases such as Alzheimer's, further implicate a role for autoimmunity and the neurodegenerative processes in glaucoma. The high correspondence of the autoantibody patterns found in the study populations from different continents provides further evidence that serum autoantibody patterns may be useful biomarkers for glaucoma detection or for determining prognosis in future studies by means of pattern-matching algorithms.

Aged↗

PubMed2005

Effect of additive preoperative latanoprost treatment on the outcome of filtration surgery.

BACKGROUND: Long-term glaucoma medication has been suspected to be a risk factor for bleb failure following trabeculectomy. It was the goal of our study to investigate whether additive preoperative treatment with latanoprost has an effect on the outcome of subsequent trabeculectomy. METHODS: We retrospectively analysed the outcome of trabeculectomy in 32 eyes of 16 patients who had received bilateral trabeculectomy within the Mainz-II study. This study had been designed to examine the effect of 6 months' use of topical latanoprost therapy on iris darkening. The first eye of each patient was operated upon without preoperative latanoprost therapy; the other eye was operated on after 6 months' treatment with latanoprost in addition to existing medical glaucoma treatment. We analysed the outcome of these patients and compared success rates and average intra-ocular pressures (IOPs) between the latanoprost-treated and the untreated partner eyes. Success was defined as an average postoperative IOP of 18 mmHg or less. RESULTS: We obtained IOP values from 13 of 16 patients, with a mean follow-up period of 6.8 years. Three patients were lost to follow-up. In both groups eight eyes (61.5%) had an average postoperative IOP (average of all IOPs measured in the follow-up period) of 18 mmHg or less. The mean average postoperative IOPs in the control group and in the latanoprost group were 15.2 mmHg and 15.8 mmHg, respectively. Intra-individual comparison revealed that one pair of eyes had equal IOPs, while six eyes in each group showed better postoperative IOP control than the respective partner eye. However, mean delta IOPs (maximum preoperative IOP minus average postoperative IOP) were 17.8 mmHg and 14.2 mmHg for the control group and latanoprost group, respectively. CONCLUSION: In this small group 6 months of additive preoperative treatment with latanoprost did not have a statistically significant effect on the success rate of trabeculectomy or on the postoperative IOP level following trabeculectomy. However, trabeculectomy in eyes preoperatively receiving latanoprost for 6 months might lead to a slightly smaller delta IOP than in eyes naive to prostaglandins.

Aged↗

PubMed2005

Effects of multipurpose contact lens solutions on the protein composition of the tear film.

OBJECTIVES: To analyze the influence of multipurpose contact lens cleaning solutions on tear proteins. Changes in tear film protein profiles of contact lens wearers who used several marketed brands of multipurpose contact lens care solutions, were assessed by ProteinChip analysis. METHODS: Three studies were conducted. Study I was a comparison of Complete and OptiFree multipurpose solutions. Study II was a study with Complete Moisture Plus solution, Study II was a comparison of Renu and Solocare contact lens solutions. Wearers of soft contact lenses were assigned to use the contact lens care solutions for 4 weeks. Non-contact lens wearing patients were used as controls. Tear samples of each participant were analyzed with the ProteinChip (SELDI-TOF) system. Multivariate statistical analysis and artificial neural networks were used to determine the tear protein profiles of each study group. RESULTS: Before starting the use of the solutions, the tear protein composition in all contact lens wearers deviated from the tear composition of the non-contact lens wearing controls. After 4 weeks of using the different care regimens, the tear protein composition of the patients using Complete or Complete Moisture Plus solutions tended to move toward that of the non-contact lens wearing controls. The tear protein composition of patients using the OptiFree, Renu or Solocare solutions did not undergo a measureable change in the protein level. CONCLUSIONS: The ProteinChip system can analyze protein profiles for large-scale applications as in clinical studies. Two multipurpose solutions, Complete and Complete Moisture Plus, demonstrated a beneficial effect on the tear proteins in contact lens wearers.

Contact Lens Solutions↗

PubMed2005

Repeatability and reproducibility of optic nerve head topography using the retinal thickness analyzer.

OBJECTIVE: The objective was to determine the reproducibility and repeatability of topographic disk parameters with the retinal thickness analyzer (RTA). METHODS: Thirty-nine eyes of 39 healthy subjects were included. Three observers performed three consecutive measurements of optic disk topography independently. Combined repeatability (intra-observer component of variability) and reproducibility (inter-observer component of variability, R and R) was assessed by variance component analysis. RESULTS: Six topographic parameters (disk area, cup area, cup volume, mean cup depth, maximum depth, and cup shape measure) revealed an acceptable repeatability and reproducibility expressed as the percentage of the total measurement variability (range 17.6-28.4%). The average reproducibility and repeatability of all optic disk parameters measured using the RTA was not acceptable (combined R and R = 33.4%). CONCLUSIONS: Repeatability and reproducibility of the optic disk topography analysis using the RTA reveals a high variation, and should, therefore, be interpreted carefully for glaucoma diagnosis and for monitoring the disease.

Adult↗

PubMed2005

Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens.

PURPOSE: The aim of this study was to analyze and compare the entire IgG autoantibody patterns against different ocular antigens (retina, optic nerve, and optic nerve head) in sera of glaucoma patients and healthy subjects. METHODS: Sixty-six patients were included in this study: healthy volunteers without any ocular disorders (CO, n=30), patients with primary open-angle glaucoma (POAG, n=19), and patients with normal-tension glaucoma (NTG, n=17). The sera were tested for antibodies against retinal, optic nerve, and optic nerve head tissues. Immunodetection was performed using 4-chloro-1-naphthol staining. The autoantibody patterns were digitized and subsequently analyzed by multivariate statistical techniques. RESULTS: All patients showed a complex repertoire of IgG antibodies against retinal, optic nerve, and optic nerve head antigens. The analysis of discriminance revealed a statistically significant differences between the patterns of all three groups. Our multivariate approach could quantify the differences in immunoreactivities of patient sera against the three antigens. The POAG group had the most significant difference against retinal antigens (P=0.0021) compared with the other antigens. In the NTG group the highest reactivity appeared against optic nerve head (P=0.00053) and optic nerve (P=0.0025). CONCLUSIONS: All groups showed different and complex antibody patterns against the three ocular tissues. These autoantibodies are highly specific for each patient group. The analysis of these patterns could provide further information about possible autoimmune mechanisms in the pathogenesis of glaucoma.

Aged↗

PubMed2005

Glaucoma studies from 1996 to 1999 in peer-reviewed journals.

BACKGROUND: Studies on glaucoma therapy were analyzed with regard to study design, diagnostic parameters and success criteria. MATERIALS AND METHODS: In 11 frequently read peer-reviewed periodicals, 101 studies published between 1996 and 1999 were chosen according to specific criteria. Design parameters, diagnostic measures and success criteria were investigated. RESULTS: Thirty-seven studies were retrospective and 64 prospective. Twenty-five studies were multicenter studies. Thirty-seven studies dealt with drug therapy, 12 with laser therapy, and 52 with surgical therapy. The study duration in 51% of the studies (n=52) was up to 1 year, in 28% (n=28) from 1 to 2 years, in 17% (n=17) over 2 years, and in 5% (n=5) in excess of 4 years. Four studies gave insufficient data. Forty-one studies recruited less than 50 patients and 57 studies recruited less than 75 patients. Thirty-four studies included more than 100 patients and 11 studies more than 250 patients. Sixty-one studies included race as a parameter. All 101 studies measured intraocular pressure (IOP). Forty-five studies explicitly described the method of tonometry. Thirteen studies measured a diurnal IOP. Forty-one studies examined the visual field, of which 30 named the method of perimetry. Only 28 studies examined the optic disc morphology. They all employed ophthalmoscopy, and two additionally employed optic disc photography. Sixty-three studies explicitly defined success criteria, establishing 95 different definitions: 74 definitions (78%) used a specified value for IOP as a success criterion. Out of the 70 definitions that gave an absolute value for IOP, 12 definitions (17%) used IOP values between 14 and 16 mmHg as the upper limit, 4 definitions (6%) used IOP values between 17 and 19 mmHg, and 54 definitions (77%) used IOP values between 20 and 22 mmHg. Out of the 26 definitions that specified a percentage IOP reduction, it was judged to be a success when the IOP was lowered by 20% or more from the starting value in ten definitions (38%), by 25% or more in three definitions (12%), and by 30% or more in 13 definitions (50%). CONCLUSIONS: Examples of prestigious studies show the necessity of observation periods of several years and demonstrate the need for a high number of participants, necessitating the cooperation of many study centers. Beside a more precise characterization of the patient collectives, clinical studies should always specify the measurement method clearly. Investigating a diurnal IOP profile to recognize changes in IOP and IOP peaks, as well as the routine determination of central corneal thickness, would be desirable. New diagnostic techniques for improved assessment of the functional and morphologic damage will gain in relevance in the future. The lack of a common definition of success reveals the complexity of the disease. However, an IOP reduction based on the degree of damage and ascertaining the target pressure seems sensible.

Databases, Factual↗

PubMed2005

Brimonidine versus dapiprazole: Influence on pupil size at various illumination levels.

PURPOSE: To evaluate the influence of dapiprazole versus brimonidine on pupil size at various illumination levels. SETTING: Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. METHODS: In randomized prospective study, 19 healthy volunteers received 2 ophthalmic solutions, dapiprazole and brimonidine, 1 in each eye, for intraindividual comparison. Before and after application, pupil diameter was measured using an infrared binocular pupillometer at 3 illumination levels (0.03, 0.82, and 6.4 lux). RESULTS: Only slight pupil dilation was observed under scotopic conditions after application of both agents. After 20 minutes, the median reduction in pupil width was 1.4 mm for brimonidine and 0.9 mm for dapiprazole. These effects were statistically significant for both agents (both P < .001). The maximum effect was observed after 40 minutes and remained stable through the next measurement at 180 minutes. Under mesopic lighting conditions, only a slight effect (<1 mm) was seen. CONCLUSIONS: Pupil mydriasis at scotopic illumination levels was reduced by both drugs in a similar fashion. Because of the slightly stronger effect of brimonidine, application of this agent 20 minutes before activities in dimly lit areas or at night may be recommended for photic phenomena following refractive surgery.

Adrenergic alpha-Agonists↗

PubMed2005

Results of the European Glaucoma Prevention Study.

OBJECTIVE: The European Glaucoma Prevention Study (EGPS) seeks to evaluate the efficacy of reduction of intraocular pressure (IOP) by dorzolamide in preventing or delaying primary open-angle glaucoma (POAG) in patients affected by ocular hypertension (OHT). DESIGN: Randomized, double-masked, controlled clinical trial. PARTICIPANTS: One thousand eighty-one patients (age, > or =30 years) were enrolled by 18 European centers. The patients fulfilled a series of inclusion criteria, including: IOP 22 to 29 mmHg; 2 normal and reliable visual fields (on the basis of mean deviation and corrected pattern standard deviation or corrected loss variance of standard 30/II Humphrey or Octopus perimetry); normal optic disc as determined by the Optic Disc Reading Center. INTERVENTION: Patients were randomized to treatment with dorzolamide or placebo (the vehicle of dorzolamide). MAIN OUTCOME MEASURES: Efficacy end points were visual field, optic disc changes, or both. A visual field change during follow-up had to be confirmed by 2 further positive tests. Optic disc change was defined on the basis of the agreement of 2 of 3 independent observers evaluating optic disc stereo slides. The safety end point was an IOP of more than 35 mmHg on 2 consecutive examinations. RESULTS: During the course of the study, the mean percent reduction in IOP in the dorzolamide group was 15% after 6 months and 22% after 5 years. Mean IOP declined by 9% after 6 months and by 19% after 5 years in the placebo group. At 60 months, the cumulative probability of converting to an efficacy end point was 13.4% in the dorzolamide group and 14.1% in the placebo group (hazard ratio, 0.86; 95% confidence interval [CI], 0.58-1.26; P = 0.45). The cumulative probability of developing an efficacy or a safety end point was 13.7% in the dorzolamide group and 16.4% in the placebo group (hazard ratio, 0.73; 95% CI, 0.51-1.06; P = 0.1). CONCLUSIONS: Dorzolamide reduced IOP by 15% to 22% throughout the 5 years of the trial. However, the EGPS failed to detect a statistically significant difference between medical therapy and placebo in reducing the incidence of POAG among a large population of OHT patients at moderate risk for developing POAG, because placebo also significantly and consistently lowered IOP.

Administration, Topical↗

PubMed2005

Is there a relationship between the degree of preoperative motility impairment or the muscle thickness and the outcome of strabismus surgery in patients with graves' orbitopathy after decompression surgery?

There is considerable controversy regarding the performance of strabismus surgery in patients with Graves' orbitopathy (GO). The spectrum of recommendations extends from variable dose-effect correlations for these procedures (Esser, 1994; Mourits et al., 1990; Nguyen et al., 2002) to individualized approaches such as passive intraoperative motility testing and postoperative adjustment of sutures (Lueder et al., 1992; Nguyen et al., 2002), and to local anesthesia for intraoperative assessment of active motility (Kalpadakis et al., 2004). Furthermore, prior decompression surgery is known to contribute to an unpredictable outcome (Eckstein and Esser, 2003; Esser, 1994). We retrospectively analyzed the charts of 34 patients undergoing strabismus surgery for this condition, with the aim to evaluate whether muscle size or preoperative muscle impairment are related to the outcome of surgery.

Decompression, Surgical↗

PubMed2005

SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye.

PURPOSE: Protein and peptides in tears play an important role in ocular surface diseases. In previous studies, changes have been demonstrated in the electrophoretic protein profiles of patients with dry eye. The purpose of this work was to determine the usefulness of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip Array (Ciphergen Biosystems, Inc., Fremont, CA) technology for the automated analysis of proteins and peptides in tear fluid. METHODS: Patients with dry eye (DRY, n = 88) and healthy subjects (CTRL, n = 71) were examined. Their tear proteins were analyzed using SELDI-TOF-MS ProteinChip Arrays with three different chromatographic surfaces (CM10 cation exchange, Q10 anion exchange, and H50 reversed-phase) prepared by means of a laboratory liquid-handling robotic workstation. The data were analyzed by multivariate statistical techniques and artificial neural networks, and the most important biomarkers were purified and identified by tandem MS. RESULTS: Complex patterns of tear proteins and peptides were detected. The different chromatographic surfaces revealed the selective enrichment of proteins such as lipocalin and lysozyme. Discriminant analysis demonstrated highly significant changes in the protein profiles in patients with dry eye (P < 0.001). With a seven-peptide multimarker panel, an artificial neural network could differentiate between patients with dry eye and healthy individuals with a specificity and sensitivity of 90%. The identification of biomarkers revealed an increase of inflammatory markers in patients with dry eye and a decrease of some proteins that may have protective functions. CONCLUSIONS: The SELDI-TOF-MS technology seems to be ideally suitable for the mass screening of peptides and proteins in tears. This highly sensitive approach dramatically reduces the analysis time and provides protein profiles with great mass accuracy. Thus, it may become a very useful tool in the search for potential biomarkers for diagnosis and new therapeutics in ocular diseases such as dry eye.

Biomarkers↗

PubMed2004

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

BACKGROUND: The 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). METHODS: Nineteen 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. RESULTS: No 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). CONCLUSIONS: DCT 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.

Aged↗