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.

The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule for diagnosing glaucomatous optic disc damage.

PURPOSE: To determine the accuracy with which the optic disc can be diagnosed as normal or glaucomatous according to the ISNT rule, whereby, in the normal eye, the neuroretinal rim area follows the order inferior (I) > superior (S) > nasal (N) > temporal (T). DESIGN: Prospective, cross-sectional, observational, case series. PARTICIPANTS: Fifty-one normal individuals and 78 individuals with open-angle glaucoma exhibiting field loss (median mean deviation, -4.37 dB; interquartile range [IQR], -2.10 to -7.96 dB; median pattern standard deviation, 5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on the basis of the appearance of the optic disc and of the corresponding visual field. METHODS: Stereoscopic optic disc photographs, acquired for each individual, were digitized at high resolution and analyzed using a digital, quad-buffered, stereoscopic viewing system in which a Z screen was used to dissociate the images to the 2 eyes of the observer. Three expert observers, trained to fellowship standard in glaucoma, independently undertook planimetry of the neuroretinal rim and of the disc margin from 1 eye of each individual, using a cursor moving in stereoscopic space to minimize parallax errors. Software automatically calculated the neuroretinal rim area in 10°, 30°, 40°, and 90° segments. For the ISNT rule to be obeyed, the 3 Boolean comparisons of the neuroretinal rim area, I>S, S>N, and N>T, had to be true. If any of the comparisons returned false, the rule was considered not to have been obeyed. Values were compared at a precision of 0.0001 mm(2). MAIN OUTCOME MEASURES: The outcome of the ISNT rule in terms of the 3 Boolean comparisons of the neuroretinal rim area was specified in terms of the sensitivity, specificity, and hence, the positive and negative likelihood ratios. RESULTS: Based on the ISNT rule being obeyed for 10° segments, the positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval [CI], 0.99-1.25), 1.07 (95% CI, 0.94-1.21), and 1.06 (95% CI, 0.96-1.18), respectively. It was similar for the other segment sizes. Variants of the rule were not appreciably better. CONCLUSIONS: The ISNT rule has limited utility in the diagnosis of open-angle glaucoma.

Detecting vigabatrin toxicity by imaging of the retinal nerve fiber layer.

PURPOSE: To quantify retinal nerve fiber layer thickness (RNFLT) and macular thickness (MT) in patients exhibiting vigabatrin-attributed visual field loss (VAVFL) and to determine the efficacy of these measures as markers of the retinal damage associated with vigabatrin. METHODS: This was a prospective cross-sectional observational study involving five groups: Group I, 13 patients exhibiting VAVFL; Group II, 8 patients exposed to vigabatrin but with normal fields; Group III, 14 patients receiving carbamazepine monotherapy; Group IV, 20 normal individuals; and Group V, 7 patients receiving sodium valproate monotherapy. At one of two visits, the right eye of each participant underwent two digital imaging modalities: ocular coherence tomography (OCT; StratusOCT; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy (SLO; Heidelberg Retinal Tomograph; Heidelberg Engineering GmbH, Heidelberg, Germany). At the other visit, participants underwent three-zone, age-corrected suprathreshold perimetry of the whole field and threshold perimetry of the central field (Humphrey Field Analyzer 750; Carl Zeiss Meditec). The order of the visits was randomized. RESULTS: The group mean RNFLT in Group I was attenuated relative to that of the remaining groups (all P < 0.001). At 100% specificity, based on the 95% confidence limits derived from Group IV, OCT exhibited 100% sensitivity and SLO 77% sensitivity for an attenuated RNFLT in patients with VAVFL. All participants manifested an MT within the normal range derived from Group IV. CONCLUSIONS: OCT of the RNFL can efficiently identify vigabatrin-induced damage and will be useful for adults and children unable to perform perimetry and when the perimetric outcome is equivocal.

Evidence for a learning effect in short-wavelength automated perimetry.

PURPOSE: To document the magnitude of any learning effect for short-wavelength automated perimetry (SWAP) in patients with either ocular hypertension (OHT) or open-angle glaucoma (OAG) who are experienced in standard automated perimetry (SAP). DESIGN: Experimental study. PARTICIPANTS: Thirty-five patients (22 with OHT and 13 with OAG) who had previously undergone at least 3 threshold SAP visual field examinations with the Humphrey Field Analyzer (HFA; Carl Zeiss Meditech Inc., Dublin, CA), and 9 patients with OHT who had not previously undertaken any form of perimetry. METHODS: Each patient attended for SWAP on 5 occasions, each separated by 1 week. At each visit, both eyes were examined using Program 24-2 of the HFA; the right eye was always examined before the left eye. MAIN OUTCOME MEASURES: (1) Change over the 5 examinations, in each eye, of the visual field indices Mean Deviation (MD), Short-term Fluctuation (SF), Pattern Standard Deviation (PSD), and Corrected Pattern Standard Deviation. (2) Change in each eye between Visits 1 and 5 in proportionate Mean Sensitivity (pMS) for the central annulus of stimulus locations compared with that for the peripheral annulus thereby determining the influence of stimulus eccentricity on any alteration in sensitivity. (3) Change between Visits 1 and 5 in the number and magnitude of the Pattern Deviation (PD) probability levels associated with any alteration in sensitivity. RESULTS: The MD, SF, and PSD each improved over the 5 examinations (each at P<0.001). The improvement in pMS between Visits 1 and 5 was greater for the peripheral annulus than for the central annulus by approximately twofold for the patients with OAG. Considerable variation was present between patients, within and between groups, in the number of locations exhibiting an improving sensitivity between Visits 1 and 5 by 1 or more PD probability levels. CONCLUSIONS: Care should be taken to ensure that, during the initial examinations, apparent field loss with SWAP in patients exhibiting a normal field by SAP is not the result of inexperience in SWAP. Apparently deeper or wider field loss in the initial examinations with SWAP compared with that exhibited by SAP in OAG also may arise from inexperience in SWAP.

A 6-week, double-masked, parallel-group study of the efficacy and safety of travoprost 0.004% compared with latanoprost 0:005%/timolol 0.5% in patients with primary open-angle glaucoma or ocular hypertension.

OBJECTIVE: The objective of this study was to directly compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% eyedrops with the fixed combination of latanoprost 0.005%/timolol 0.5% eyedrops in patients with primary open-angle glaucoma or ocular hypertension. METHODS: This was a randomized, double-masked, multicenter, parallel-group, active-controlled study. Adult subjects with open-angle glaucoma (with or without pseudoexfoliation or pigment dispersion component) or ocular hypertension were eligible to participate if their IOP was inadequately controlled with > or =4 weeks of beta-blocker monotherapy, as indicated by IOP of 22 to 36 mm Hg at 9 AM at screening. Patients were randomly assigned in a 1:1 ratio to receive placebo + travoprost or latanoprost/timolol + placebo. Patients in the travoprost group administered travoprost at 9 PM and placebo at 9 AM; patients in the latanoprost/timolol group administered latanoprost/timolol at 9 AM and placebo at 9 PM. IOP measurements were performed using Goldmann applanation tonometry at 9 AM and 5 PM at the week-2 and week-6 visits. Both volunteered and elicited reports of adverse events were collected; all patients who were randomized and received > or =1 dose of study drug were included in the safety analysis. RESULTS: One hundred ten patients were randomized, of whom 106 patients were evaluable (travoprost, n = 50; latanoprost/timolol, n = 56). There were no statistically significant differences at baseline between the treatment groups, based on age group, sex, race, iris color, or diagnosis. Mean IOP values were not statistically different between groups at baseline or during treatment. In the pooled results for 9 Am assessment at weeks 2 and 6, mean (SEM) IOP reductions for travoprost and latanoprost/timolol were 7.0 (0.5) and 6.4 (0.5) mm Hg, respectively (P = NS). Adverse events related to therapy were mild in nature, and there were no statistically significant differences between the 2 treatment groups. The most frequently experienced adverse events in the travoprost group were ocular hyperemia (9.3%), foreign body sensation (5.6%), abnormal vision (1.9%), allergic reaction (1.9%), conjunctivitis (1.9%), dacryocystitis (1.9%), eye discharge (1.9%), eye pruritus (1.9%), lid edema (1.9%), lid erythema (1.9%), and tearing (1.9%). In the latanoprost/timolol group, the most frequently experienced adverse events were cataract (1.8%), dry eyes (1.8%), eye pruritus (1.8%), foreign body sensation (1.8%), and ocular hyperemia (1.8%). CONCLUSIONS: Mean IOP changes from baseline for travoprost 0.004% and latanoprost 0.005%/timolol 0.5% fixed combination were not significantly different at follow-up in these patients. Both medications were well tolerated.

Higher order aberrations with aspheric ablations using the Nidek EC-5000 CX II laser.

PURPOSE: To analyze the change in higher order aberrations in myopic and myopic astigmatic eyes following an aspheric ablation profile for laser in situ keratomileusis (LASIK) using a Nidek EC-5000 CX II excimer laser system. METHODS: We performed a retrospective audit of 38 eyes (19 patients) with myopia and myopic astigmatism. A customized aspheric transition zone profile (CATz) was used in all eyes (profile 4) with an ablation zone of 5 mm and a transition zone of 9 mm using FinalFit software and a Nidek EC-5000 CX II excimer laser system. RESULTS: Mean higher order aberrations (RMS) increased from 0.42 microm at baseline to 0.57 microm at 6-month follow-up. Mean spherical aberrations (Z12) increased from 0.02 microm at baseline to 0.33 microm after LASIK. Mean spherical aberration defocus equivalent (DEQ) increased from 0.56 microm at baseline to 1.54 at 6 months after surgery. Mean trefoil (Z6) was -0.11 microm at baseline and -0.14 microm at the 3-month examination. Mean coma (Z7) was -0.09 microm at baseline and -0.10 microm after surgery. Mean coma (Z8) was -0.03 at baseline and 0 at the 3-month examination. Mean trefoil (Z9) was -0.03 at baseline and -0.12 at the 3-month examination. CONCLUSION: The amount of postoperative higher order aberrations in these myopic eyes was acceptable. However, the clinical significance of these numerical changes in aberrations is not known.

Correlation of Nidek OPD-Scan objective refraction with subjective refraction.

PURPOSE: The aim of this study was to quantify how closely the Nidek OPD-Scan objective refraction correlated with subjective refraction. METHODS: A retrospective audit of the preoperative refraction of 80 myopic and myopic astigmatic eyes before laser in situ keratomileusis (LASIK) or laser supepithelial keratomileusis (LASEK) was performed. Objective refraction in the 5-mm zone was performed using a Nidek OPD-Scan. Subjective refraction was performed by a senior optometrist. Statistical analysis of sphere, cylinder, and spherical equivalent refraction measurements was then performed. RESULTS: Spherical measurements correlated well with a linear regression equation, with a correlation coefficient of 0.97. Cylinder measurements correlated less well, with a correlation coefficient of 0.85. Spherical equivalent refraction measurements correlated well, with a correlation coefficient of 0.97. Analyzing the numerical difference between each objective refraction and its corresponding subjective refraction, the majority of values were only 0.50 D apart for sphere, cylinder, and spherical equivalent refraction. CONCLUSION: There was good correlation between objective OPD-Scan and subjective refraction, especially for sphere and spherical equivalent refraction measurements, with regression gradients and correlation coefficients close to 1.

Rare case of post-cataract-surgery Prevotella endophthalmitis diagnosed by polymerase chain reaction DNA sequencing.

We report the presentation, diagnosis, and management of endophthalmitis caused by the opportunistic Prevotella species. The case was referred to us following uneventful phacoemulsification and intraocular lens implantation. Accurate identification of this rare cause of endophthalmitis was made using bacterial polymerase chain reaction DNA sequencing. Subsequent prompt modification of antibacterial therapy allowed resolution of signs and symptoms and significant visual recovery. To our knowledge, this is the first reported case of diagnosis and management of post-cataract-surgery endophthalmitis caused by the opportunistic Prevotella species.