Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

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.

Outcomes of different management options for malignant glaucoma: a retrospective study.

BACKGROUND: To assess the outcomes of the various medical and surgical treatment options for malignant glaucoma. METHODS: Design Retrospective, comparative case series. Participants Twenty-four eyes of 21 patients with malignant glaucoma. Intervention Nine eyes were treated medically. Twenty-one eyes underwent surgery, 15 of which had the full vitrectomy-(phaco)-iridectomy-zonulectomy procedure. Main outcome measures Intraocular pressure (IOP), best-corrected visual acuity (BCVA) and number of glaucoma medications were measured. RESULTS: The relapse rate was 100% after medical therapy, 75% after a Yag laser capsulotomy and a hyaloidotomy, 75% after a conventional vitrectomy and 66% after an anterior vitrectomy in combination with an iridectomy-zonulectomy. All patients who underwent a full vitrectomy combined with an iridectomy and a zonulectomy (and phacoemulsification if phakic) had postoperative relief of malignant glaucoma without relapse within the follow-up period. After this vitrectomy-tunnel technique, the IOP ranged from 10 to 22 mmHg (mean 16 mmHg) after a mean follow-up of 61 days. Mean BCVA improved by 5 Early Treatment Diabetic Retinopathy Study (ETDRS) lines, and mean number of glaucoma medications decreased from two to one. CONCLUSION: Complete vitrectomy combined with iridectomy and zonulectomy (and phacoemulsification, if applicable) most successfully managed aqueous misdirection syndrome in our retrospective case series.

Agreement and accuracy of non-expert ophthalmologists in assessing glaucomatous changes in serial stereo optic disc photographs.

PURPOSE: To compare the interobserver agreement in detecting glaucomatous optic disc changes using serial stereophotography between a large group of non-expert ophthalmologists and glaucoma specialists; to assess the accuracy of non-experts; to investigate whether the interobserver agreement and the accuracy of non-experts changed after a training session. DESIGN: Masked interobserver agreement study. PARTICIPANTS: Serial optic disc stereophotos from 40 patients with glaucoma. METHODS: Three independent experienced glaucoma specialists (readers of the European Glaucoma Prevention Study) evaluated a set of 2 serial optic disc color stereo-slides for glaucomatous change, obtained with a delay varying from 2 to 7 years of 40 patients, masked from the temporal sequence of the slides. Each patient was graded as changed or stable by agreement of 2 of 3 of the experts (the reference standard). Thirty-seven non-expert ophthalmologists independently evaluated the same set of serial optic disc stereo-slides twice, with the second evaluation on the same day, masked from the results of the previous evaluation, after a training session on a separate slide set. MAIN OUTCOME MEASURES: Interobserver agreement of non-experts and experts in detecting glaucomatous optic disc changes (expressed as kappa coefficient); agreement of non-experts with the reference standard (accuracy) before and after a training session. RESULTS: The interobserver kappa coefficient (κ) of the non-experts and experts was 0.20 (95% confidence interval [CI], 0.19-0.21) and 0.51 (95% CI, 0.33-0.69), respectively (P<0.0001). The mean κ of the non-experts with the reference standard was 0.33 (95% CI, 0.27-0.39). After a training session, the interobserver agreement of the non-experts increased from 0.20 to 0.27 (95% CI, 0.26-0.28) (P<0.0001). The percentage agreement of the non-experts with the reference standard improved from 68.5% before to 71.4% after the training session (Wilcoxon signed-rank test, P=0.034). CONCLUSIONS: The interobserver agreement of non-expert ophthalmologists in detecting glaucomatous optic disc changes using serial stereophotos was significantly lower than that of experts, which was moderate. After a training session, the interobserver agreement and the accuracy of the non-experts showed a small but statistically significant improvement.

Preoperative nonsteroidal anti-inflammatory drug or steroid and outcomes after trabeculectomy: a randomized controlled trial.

PURPOSE: To investigate the benefit of preoperative treatment with either topical nonsteroidal anti-inflammatory drug (NSAID) or steroid in terms of clinical outcomes following trabeculectomy. DESIGN: Prospective, randomized placebo-controlled trial. PARTICIPANTS: Sixty-one patients. METHODS: Between July 2005 and October 2007, 61 consecutive medically uncontrolled glaucoma patients scheduled for first-time trabeculectomy were randomized to 1 of 3 study topical medication groups: nonsteroidal anti-inflammatory drugs (ketorolac), steroids (fluorometholone), or placebo (artificial tears). Patients instilled 1 drop 4 times daily for 1 month before the procedure and were examined on days 1 and 2, at weeks 1, 2, and 4, and at months 3, 6, 12, 18, and 24 after trabeculectomy. MAIN OUTCOME MEASURES: Incidence of postoperative surgical or medical interventions (needling, laser suture lysis, needling revision, and intraocular pressure [IOP]-lowering medication). RESULTS: Fifty-four patients (54 eyes) were entered for analysis. The mean number of preoperative medications was 2.3+/-0.9. The mean baseline IOP was 21.0+/-6.0 mmHg. The mean postoperative target IOP was 16.5+/-1.8 mmHg. The mean follow-up was 23.6+/-4.0 months. The percentage of patients requiring needling within the first year was 41% in the placebo group, 6% in the NSAID, and 5% in the steroid group (P = 0.006). The percentage of patients requiring IOP-lowering medication to reach the target IOP at 1 year was 24% in the placebo group, 18% in the NSAID group, and 0% in the steroid group (P = 0.054 overall; P = 0.038 for steroids vs. others). The log-rank test showed a significant (P = 0.019) difference in medication-free survival curves between the different groups. More specifically, patients in the steroid group needed significantly less medication over the total follow-up (P = 0.007). CONCLUSIONS: Topical ketorolac or fluorometholone for 1 month before surgery was associated with improved trabeculectomy outcomes in terms of likelihood of postoperative needling. In the steroid group, there was a significantly reduced need for additional postoperative IOP-lowering medication compared with the other groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Comparison of ocular response analyzer, dynamic contour tonometer and Goldmann applanation tonometer.

The aim of this study was to compare the intra-ocular pressure (IOP) obtained by ocular response analyzer (ORA), dynamic contour tonometer (DCT) and Goldmann applanation tonometer (GAT). In 102 patients (47 with primary open-angle glaucoma and 55 healthy controls) IOP was measured with GAT, ORA and DCT in one eye. The agreement between GAT, DCT and ORA values was assessed using Bland-Altman plots. The discrepancy between the methods was related to central corneal thickness (CCT), corneal hysteresis (CH) and corneal resistance factor (CRF) using linear regression models. Significant differences were observed amongst DCT, corneal compensated ORA (ORAcc) and GAT (P < 0.01). Only the ORAcc and DCT were comparable. ORAcc and DCT significantly over-estimated IOP compared to GAT and for ORAcc this difference depended on the height of IOP. A significant correlation was found between CCT and the deviation of DCT and ORAcc from corrected GAT (both P < 0.0001). Our study showed a low degree of agreement between IOP measured by ORA, DCT and GAT. DCT and ORAcc over-estimated the IOP compared to GAT.

Reproducibility of color Doppler imaging.

PURPOSE: The aims of this study were: (1) to determine the intra-subject and inter-observer variability of color Doppler imaging (CDI) measurements and readings of the retrobulbar blood vessels, (2) to compare the difference invariability of CDI parameters in non-glaucomatous controls versus glaucoma patients, and (3) to provide calculations of minimum sample sizes for future CDI studies. METHODS: Patients with normal tension glaucoma (n=28), primary open-angle glaucoma (n=19) and non-glaucomatous controls of comparable age (n=22) underwent CDI on two occasions 1 month apart. Variability in CDI parameters was quantified using (within-subject) coefficients of variation. Based on this variability, minimum sample sizes were calculated to guide the design of future studies comparing CDI between and within groups. RESULTS: In general, within-subject coefficients of variation for measurements 1 month apart were comparable to previously reported short-term variations. Variability was higher in glaucoma patients than in non-glaucomatous controls. The minimum sample size required for glaucomatous study populations is larger than for non-glaucomatous controls. Smaller patient groups are required to detect change using the peak systolic blood flow velocities than using end diastolic velocities. Studies using a cross-over design require smaller sample sizes than studies with a prepost or particularly parallel design. CONCLUSIONS: This study provides extensive information on long-term intra-subject variability of CDI measurements in non-glaucomatous controls as well as glaucoma patients. Moreover, sample size calculations are provided for studies involving glaucoma patients as well as non-glaucomatous individuals, using three different commonly used study designs.

Comparison of ICare, dynamic contour tonometer, and ocular response analyzer with Goldmann applanation tonometer in patients with glaucoma.

PURPOSE: To compare the intraocular pressure (IOP) readings taken by ICare, Pascal dynamic contour tonometer (DCT), and ocular response analyzer (ORA) with those taken by Goldmann applanation tonometer (GAT). We sought to evaluate the influence of central corneal thickness (CCT) on IOP measurements and to compare patients' preferences for the four tonometers. METHODS: In this prospective study, 93 eyes from 93 patients were examined. Patients were randomly divided into 4 groups to vary the order in which the tonometers were applied. CCT was measured with an ultrasound pachymeter. RESULTS: The average CCT was 558+/-47.4 microm. The mean +/- standard deviation IOP for GAT, ICare, DCT, and ORA (Goldmann-correlated IOP) (ORA(GC)) were 15.1+/-4.8, 15.7+/-5.7, 18.2+/-5.1, and 18.3+/-6.6 mmHg, respectively. There was no significant difference between the mean IOP obtained with GAT and ICare (p=0.14). There was also no difference in IOP levels between the mean IOP obtained with DCT and ORA (p=0.26). There was no correlation between IOP measurements and CCT for the 4 instruments. Bland-Altman graphs showed disagreement between the measurements taken by GAT and the other instruments. There was no significant difference in patients' preference among the 4 instruments (p=0.48). CONCLUSIONS: IOP readings from ICare were consistent with those from GAT, whereas DCT readings correspond well to ORA(GC) measurements. DCT and ORA readings both overestimated the GAT readings. There was no correlation between the IOP measurements and the CCT for the 4 instruments. There was no significant difference in patients' preference among the 4 instruments.

Color Doppler imaging and ocular pulse amplitude in glaucomatous and healthy eyes.

PURPOSE: To determine factors influencing color Doppler imaging (CDI) measurements, to compare retrobulbar flow velocities between patients with glaucoma and healthy controls, and to describe the correlation between CDI and ocular pulse amplitude (OPA). METHODS: Patients with normal tension (n=28) or primary open angle glaucoma (n=19) and healthy controls (n=22) underwent CDI and OPA measurements. Intraocular pressure, corneal thickness, blood pressure, and heart rate were also measured. Spearman correlations were used to explore relations among these variables. A regression model for repeated measures was applied to compare between diagnostic groups the flow velocity indices in the retrobulbar vessels. RESULTS: Retrobulbar diastolic blood flow velocities correlated with diastolic blood pressure and perfusion pressure (range of Spearman rho [rho] coefficients=0.25-0.28; p=0.044-0.013 for the different vessels). Corneal thickness showed a positive correlation with systolic and diastolic flow velocities in the central retinal artery (rho=0.29 and 0.31; p=0.017 and 0.011 for peak systolic and end diastolic velocity, respectively). Systolic and diastolic blood flow velocities were reduced in the retrobulbar vessels of patients with normal tension glaucoma (P=0.0004) as well as primary open angle glaucoma (P=0.003) compared to healthy controls. A correlation was found between OPA and the resistive index in the retrobulbar vessels of the healthy controls (range rho=0.42-0.53; p=0.059-0.014). CONCLUSIONS: Retrobulbar blood flow velocities are reduced in patients with primary open angle glaucoma and normal tension glaucoma. Blood pressure and corneal thickness may influence CDI measurements. OPA correlates with the resistive index in CDI.

The safety and efficacy of glaucoma medication in the pediatric population.

Topical glaucoma medications are widely used for childhood glaucoma, although little is known concerning the use of the newer glaucoma medications in this population. The majority of the references cited were extracted from PubMed. A literature review of all English language reports related to glaucoma medication in the pediatric population since 1980 was performed. Medical therapy of pediatric glaucoma contains four groups of drugs: beta-blockers (timolol and betaxolol), carbonic anhydrase inhibitors (dorzolamide), alpha2-agonists (brimonidine), and prostaglandin analogs (latanoprost). Timolol is the first choice in pediatric glaucoma. In cases with insufficient reduction of the intraocular pressure (IOP), the combination of timolol once a day and dorzolamide twice a day brings about a good control of the IOP. Both medications are effective and well tolerated. The alpha2-agonists have more and potentially serious adverse effects in children and are contraindicated for children younger than 2 years of age. Latanoprost tends to be less effective in lowering IOP in children than in adults. However, no studies are reported where latanoprost is used in monotherapy. Additional study may further delineate this drug's role in treating pediatric glaucoma. The safety profile of latanoprost in children appears excellent.

Detection of glaucomatous change based on vessel shape analysis.

Glaucoma, a leading cause of blindness worldwide, is a progressive optic neuropathy with characteristic structural changes in the optic nerve head and concomitant visual field defects. Ocular hypertension (i.e. elevated intraocular pressure without glaucoma) is the most important risk factor to develop glaucoma. Even though a number of variables, including various optic disc and visual field parameters, have been used in order to identify early glaucomatous damage, there is a need for computer-based methods that can detect early glaucomatous progression so that treatment to prevent further progression can be initiated. This paper is focused on the description of a system based on image processing and classification techniques for the estimation of quantitative parameters to define vessel deformation and the classification of image data into two classes: patients with ocular hypertension who develop glaucomatous damage and patients with ocular hypertension who remain stable. The proposed system consists of the retinal image preprocessing module for vessel central axis segmentation, the automatic retinal image registration module based on a novel application of self organizing maps (SOMs) to define automatic point correspondence, the retinal vessel attributes calculation module to select the vessel shape attributes and the data classification module, using an artificial neural network classifier, to perform the necessary subject classification. Implementation of the system to optic disc data from 127 subjects obtained by a fundus camera at regular intervals provided a classification rate of 87.5%, underscoring the value of the proposed system to assist in the detection of early glaucomatous change.

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.

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.

Intercurrent factors associated with the development of open-angle glaucoma in the European glaucoma prevention study.

PURPOSE: To evaluate the intercurrent factors for the development of open-angle glaucoma (OAG) in ocular hypertensive patients who were enrolled in the European Glaucoma Prevention Study (EGPS). DESIGN: Randomized, double masked, controlled clinical trial. METHODS: setting: Multicenter. study population: A total of 1,077 patients fulfilled a series of inclusion criteria, including intraocular pressure (IOP) 22 to 29 mm Hg, normal and reliable visual fields (VFs) and normal optic disks. intervention: Treatment with dorzolamide or placebo. main outcome measures: Glaucoma-related VF or optic disk changes. Clinical data were collected every six months during a five-year follow-up. Proportional hazards models were used to identify the factors that during follow-up (intercurrent factors) were associated with the development of OAG. RESULTS: In multivariate analyses, adjusting for treatment arms and baseline predictive factors, mean follow-up IOP reduction (hazard ratio [HR] 0.89, 95% confidence intervals [CI] 0.80 to 0.98), mean follow-up IOP (HR 1.12, 95% CI 1.03 to 1.22), area under the curve of IOP (mm Hg per year) (HR 1.09, 95% CI 1.06 to 1.12), disk hemorrhages (HR 1.97, 95% CI 1.21 to 3.22), and use of systemic diuretics (HR 2.41, 95% CI 1.12 to 5.19) were associated with the development of OAG. Baseline central corneal thickness, vertical cup/disk ratio, vertical cup/disk ratio asymmetry, and pattern standard deviation remained statistically significant. CONCLUSIONS: These results suggest the need for future investigations to better elucidate the role of systemic diuretics in the development of OAG, because IOP and disk hemorrhages have already been shown to be important intercurrent factors in the Ocular Hypertension Treatment Study (OHTS) and Early Manifest Glaucoma Trial (EMGT).

Precipitation of calcium salts on a hydrophilic acrylic intraocular lens after a vitreous hemorrhage: case report and histopathologic correlation.

We describe the formation of calcium phosphate deposits on the external anterior surface of a single-piece foldable 26% hydrophilic acrylic intraocular lens (IOL) after vitreal bleeding. The IOL was explanted 20 months after uneventful phacotrabeculectomy because opacification was causing significant visual disturbance. Light microscopy and Raman spectroscopy of the explanted IOL showed that the opacification consisted of calcium phosphate on the IOL surface.

The Effect of Trabeculectomy on Astigmatism.

PURPOSE: To investigate the change in corneal astigmatism after trabeculectomy. PATIENTS AND METHODS: Between January and April 2012, patients who underwent a primary trabeculectomy were enrolled in this prospective study. We measured the visual acuity, automated keratorefractometry, and the intraocular pressure preoperatively and postoperatively at 1, 3, and 6 months. Changes in astigmatism were quantified using the vector analysis described by Cravy. A Friedman test and a linear model for longitudinal measures were used to compare changes in the refraction and the intraocular pressure. A binomial test was used to compare the proportion of eyes with a shift in astigmatism with or against-the-rule. RESULTS: A total of 47 eyes (47/48 patients) were included for analysis. The mean (±SD) intraocular pressure decreased from 17.5 ± 5.4 mmHg preoperatively to 9.8 ± 4.0 mmHg after 6 months (P<0.001). At this time-point, 32/47 eyes showed a shift in astigmatism with-the-rule (P=0.02), with a median difference in cylinder of +0.50 D (range, 0 to 4 D) (P=0.004). The mean (±SD) axis of the positive cylinder changed from 169 ± 148 to 135 ± 146 degrees after 6 months (P=0.12) and the mean (±SD) spherical equivalent changed from -0.47 ± 2.27 to -0.07 ± 1.93 D (P=0.15). The mean (±SD) logMAR was 0.17 ± 0.22 preoperatively and 0.14 ± 0.14 after 6 months (P=0.9). CONCLUSIONS: Trabeculectomy induced a small but statistically significant shift in astigmatism with-the-rule after 6 months. The spherical equivalent did not change compared with the preoperative value. Most often, glasses will not need to be changed after trabeculectomy.

The Conjunctiva in Normal Tension Glaucoma Patients is Thinner Than in Primary Open-Angle Glaucoma Patients: A Comparative Histologic Study.

PURPOSE: To compare histologically the thickness of conjunctival specimens of normal tension glaucoma (NTG) patients with primary open-angle glaucoma (POAG) patients. MATERIALS AND METHODS: In this prospective study, 54 patients scheduled for trabeculectomy were categorized into NTG and POAG based on their maximum untreated intraocular pressure at any time (IOPmax) as measured by Goldmann applanation tonometry. Sixteen patients with NTG (IOPmax≤21 mm Hg) and 36 patients with high tension POAG (IOPmax>21 mm Hg) were included in the study. Biopsies were taken from the superior bulbar conjunctiva during trabeculectomy. The specimens were fixed in formalin, embedded in methacrylate, histologically sectioned, stained with toluidine blue, and analyzed with a light microscope. The stromal conjunctival thickness (CT) was measured in a standardized way and compared between the 2 groups. Intergroup comparisons were performed using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. The correlation between the central cornea thickness (CCT) and the CT was investigated by the Spearman test. RESULTS: The stromal CT was significantly thinner in NTG compared with POAG (64±31 vs. 103±44 µm, respectively; P=0.002). Stromal CT of the whole group was positively correlated with IOPmax (r=0.41; P=0.002; 95% confidence interval, 0.15-0.62) but not with central cornea thickness (r=-0.005; P=0.97; 95% confidence interval, -0.28 to 0.27). CONCLUSIONS: The conjunctiva in patients with NTG was thinner than in POAG patients. This finding is an additional feature in the pattern of thinner ocular structures in patients with NTG.

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.

Sequential office pressure measurements in the management of glaucoma.

PURPOSE: To evaluate the usefulness of day-long sequential office measurements of intraocular pressure (IOP) to make therapeutic decisions in patients with progressive glaucomatous damage despite apparently 'controlled' IOP. METHODS: We reviewed the records of 93 consecutive glaucoma patients (185 eyes) who underwent sequential office IOP measurements (every hour from 7 AM to 5 PM on a single day). These included 53 patients with normal-tension glaucoma (NTG), 12 glaucoma suspects (GS), and 28 patients with primary open-angle glaucoma (POAG) whose visual field deteriorated despite apparently 'controlled' IOP. Only one eye per patient was included in the study. RESULTS: The pattern of the day-long IOP curve was similar in the 3 groups of patients. IOPs were highest in the early morning hours in all groups. The mean +/- SD of the IOP range was 5 +/- 2 mm Hg. An IOP > 21 mm Hg was found in 3 eyes (3%), whereas a range of IOPs > 5 mm Hg was detected in 33 eyes (35%). In the NTG group, there was a significant correlation between visual field deterioration and the peak and range of IOP (P = 0.0002 and P = 0.05, respectively). CONCLUSIONS: Day-long sequential office IOP measurements are useful in selected patients who demonstrate progressive glaucomatous damage. Early morning measurements are most frequently highest. The range of IOP may be as important, or more important than, the peak IOP level.