Comparative Study Between the SORS and Dynamic Strategy Visual Field Testing Methods on Glaucomatous and Healthy Subjects.

Purpose: To clinically validate the noninferiority of the sequentially optimized reconstruction strategy (SORS) when compared to the dynamic strategy (DS). Methods: SORS is a novel perimetry testing strategy that evaluates a subset of test locations of a visual field (VF) test pattern and estimates the untested locations by linear approximation. When testing fewer locations, SORS has been shown in computer simulations to bring improvements in speed over conventional perimetry tests, while maintaining acquisition at high-quality acquisition. To validate SORS, a prospective clinical study was conducted at the Department of Ophthalmology of Bern University Hospital, over 12 months. Eighty-three subjects (32 healthy and 51 glaucoma patients with early to moderate visual field loss) of 114 participants were included in the study. The subjects underwent perimetry tests on an Octopus 900 (Haag-Streit, Köniz, Switzerland) using the G pattern with both DS and SORS. The acquired sensitivity thresholds (ST) by both tests were analyzed and compared. Results: DS-acquired VFs were used as a reference. High correlations between individual STs (r ≥ 0.74), as well as between mean defect values (r ≥ 0.88) given by DS and SORS were obtained. The mean absolute error of SORS was under 3 dB with a 70% reduction in acquisition time. SORS overestimated healthy VFs while slightly underestimating glaucomatous VFs. Qualitatively, SORS acquisition yielded VF with detectable defect patterns, albeit some isolated and small defects were occasionally missed. Conclusions: This clinical study showed that for healthy and glaucomatous patients, SORS-acquired VFs sufficiently correlated with the DS-acquired VFs with up to 70% reduction in acquisition time. Translational Relevance: This clinical study suggests that the novel perimetry strategy SORS could be used in routine clinical practice with comparable utility to the current standard DS, whereby providing a shorter and more comfortable perimetry experience.

Retrograde Maculopathy in Patients With Glaucoma.

PURPOSE: Macular optical coherence tomography (OCT) analysis can be used for quantitative measures of optic nerve atrophy at a location far from the optic nerve head. This recently led to the finding of microcystic macular edema (MME), that is vacuolar inclusions in the macular inner nuclear layer, in some glaucoma patients. The involvement of individual retinal layers is yet unclear in glaucoma. In this study we systematically investigated glaucoma-induced changes in macular layers to evaluate whether glaucoma-associated damage extends beyond the macular ganglion cell layer. PATIENTS AND METHODS: We included 218 consecutive patients and 282 eyes with confirmed primary open-angle glaucoma or pseudoexfoliation glaucoma, and macular OCT in a cross-sectional observational study. Eyes were screened for presence of MME. Thickness of individual retinal layers was determined using a semiautomatic segmentation algorithm. Peripapillary nerve fiber layer thickness and mean defect in visual field testing were extracted from OCT and medical records, respectively. Results were compared with a small group of eyes with no apparent glaucoma. RESULTS: We found MME in 5 eyes from 5 primary open-angle glaucoma patients and 3 eyes of 3 pseudoexfoliation glaucoma patients (2.8%). MME was confined to the inner nuclear layer in a perifoveal ring and was associated with thinning of the ganglion cell layer and thickening of the macular inner nuclear layer. Glaucoma eyes without MME showed a significant inverse correlation of inner nuclear layer thickness with glaucoma severity. CONCLUSIONS: Glaucomatous damage leads to a gradual thickening of the inner nuclear layer, which leads to MME in more severe glaucoma cases. These changes, along with nerve fiber loss and ganglion cell loss, may be summarized as glaucoma-associated retrograde maculopathy.

A combined analysis of four observational studies evaluating the intraocular pressure-lowering ability and tolerability of bimatoprost 0.01% in patients with primary open-angle glaucoma or ocular hypertension.

OBJECTIVE: Combine and evaluate data from four clinical practice studies investigating the intraocular pressure (IOP)-lowering ability, tolerability of and patient adherence to bimatoprost 0.01% therapy in patients with primary open-angle glaucoma or ocular hypertension. METHODS: Data were combined from four multicenter, prospective, observational studies. Patients (n=2,593) were recruited from 328 sites in Austria, Belgium, Switzerland, and the Netherlands. Assessments were at study entry (baseline) and after 10-14 weeks. RESULTS: Bimatoprost 0.01% lowered mean IOP by 5.0 mmHg from baseline to final visit (P<0.0001). Individual IOP goals were achieved in 75.5% of patients. Results were similar in right and left eyes; right-eye data are presented here for brevity. The greatest mean IOP reduction was 6.7±4.7 mmHg (28.8% reduction from baseline to final visit, P<0.0001) in treatment-naïve patients. Switching to bimatoprost 0.01% monotherapy from previous monotherapy reduced mean IOP by a further 3.2±3.6 mmHg (17.2%, P<0.0001). Switching to bimatoprost 0.01% from previous prostaglandin monotherapy reduced mean IOP by 2.9±3.5 mmHg (15.5%), including by 3.1±3.4 mmHg (15.8%) and 3.3±4.1 mmHg (16.9%) for previous latanoprost and travoprost treatment, respectively (all P<0.0001). IOP reduction in patients previously treated with a fixed combination was 2.7±4.0 mmHg (14.2%, P<0.0001). The most commonly reported adverse events were conjunctival hyperemia (5.2%) and eye irritation (4.7%). Tolerability was rated as "very good" or "good" by 90.1% of patients. Adherence was rated by physicians as "better than" or "equal to" previous treatment in 97.2% of patients. CONCLUSION: The combined studies demonstrated in a clinical practice setting, bimatoprost 0.01% lowered IOP effectively in treatment-naïve and previously treated ocular hypertension and primary open-angle glaucoma patients, and was associated with good tolerability and patient adherence over 12 weeks.

Compliance and knowledge about glaucoma in patients at tertiary glaucoma units.

To document the rate of self-reported compliance and glaucoma-related knowledge in Swiss patients and to identify risk factors for their poor compliance. This was an observational study, including a total of 200 consecutive patients already under glaucoma medication in two Swiss tertiary glaucoma clinics (Geneva and Bern). Personal characteristics, presence of systemic disease, compliance with glaucoma medication, attitude to the ophthalmologist, and glaucoma-related attitudes were ascertained by means of a predetermined questionnaire with 40 questions. Patients were subsequently assessed for the ability to correctly instil placebo eye drops. Non-compliance with glaucoma medication was defined as omitting more than two doses a week as reported by the patient. Logistic regression was used to evaluate how patient characteristics and knowledge about the disease were related to compliance. Overall, 81% (n = 162) of patients reported to be compliant. Forgetfulness was the most frequently cited reason for non-compliance with dosing regimen (63%). Although 90.5% (n = 181) of patients believed glaucoma medication to be efficient, only 28% (n = 56) could correctly define glaucoma. Factors positively associated with compliance were 'knowledge of glaucoma' [adjusted odds ratio (OR) 4.77 (95% CI 1.36-16.70)] and 'getting help for administration of drops' [OR 2.95 (1.25-6.94)]. These findings indicate that despite the comparatively high compliance rate among glaucoma patients, knowledge of glaucoma remains poor in long-term glaucoma sufferers. Improving knowledge about the disease is important since it is positively associated with compliance in our study.

Pressure-cornea-vascular index (PCVI) for predicting disease progression in normal tension glaucoma.

BACKGROUND: It has been shown that the pressure-to-cornea index (PCI), which estimates the relative effects of intraocular pressure (IOP) and central corneal thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The authors investigated the utility of the pressure-cornea-vascular index (PCVI) in predicting field-progression in patients with normal tension glaucoma (NTG). METHODS: PCVI was constructed from PCI (maximum IOP/CCT(3)) extended with risk factors identified as associated with field-progression in a prospective NTG cohort. Receiver operator characteristics and area under the curve (AUC) of a range of constructs were calculated to arrive at an optimal PCVI. RESULTS: 415 eyes from 415 NTG subjects (184 field-progressed and 231 field-stable) with 3 years of follow-up were analysed. The construct PCVI=(maximum pretreatment office IOP × age at presentation × vertical cup-to-disc ratio at presentation × (1.5 if presence of systemic hypertension; 2.5 if presence of disc haemorrhage; 3.5 if presence of both; 1.0 if none))/(CCT(3)×100) (CCT in mm) gave the highest AUC at 0.71 (95% CI 0.66 to 0.76, p<0.001). The mean PCVI were 113.1±76.8 and 69.7±39.7 for progressed and stable NTG groups, respectively (p<0.001). CONCLUSION: PCVI may be useful for predicting progression in NTG with a satisfactory AUC comparable to established scoring systems in neurovascular medicine. Validation of PCVI in other NTG cohorts, preferably of different ethnicity, is necessary. Trial registration number NCT00321386.

Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments.

PURPOSE: To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements. METHODS: Six different OCT instruments (Stratus OCT [Carl Zeiss Meditec, Inc. Dublin, CA], SOCT Copernicus [Reichert/Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], RTVue-100 [Optovue Corp., Fremont, CA], Spectralis HRA+OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.]) were used to assess CRT in both eyes of healthy subjects. Measurements were performed in two different sessions on the same day with each of the systems. From these measurements, the mean CRT was calculated. For the assessment of the intersession reproducibility of the instruments, we calculated the coefficient of the variation of test-retest variation. RESULTS: Twenty healthy subjects were included in the study. Compared with the Stratus OCT all spectral OCT instruments showed significantly higher CRTs. The Spectralis HRA+OCT and Cirrus HD-OCT showed similar CRT values but significantly higher values than did all other instruments. The coefficients of variation for repeated measurements was 3.33% for the Stratus OCT, 0.46% for the Spectralis HRA+OCT, 3.09% for the Cirrus HD-OCT, 2.23% for the OCT/SLO, 2.77% for the RTVue-100 OCT, and for the SOCT 3.5%, respectively. discussion. The six OCT systems provided different results for CRT. The measurements with the Stratus OCT showed the lowest thicknesses, whereas those with the Cirrus HD-OCT and Spectralis HRA+OCT yielded the highest ones. These discrepancies can be explained by the differences in the retinal segmentation algorithms used by the various OCT systems. Whereas the Spectralis HRA+OCT and Cirrus HD-OCT include the RPE layer in the retinal segmentation, the other instruments do not. The data imply that the different OCT systems cannot be used interchangeably for the measurement of macular thickness.

Dynamic contour tonometry in keratoconus and postkeratoplasty eyes.

PURPOSE: To compare the performance of dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT) in measuring intraocular pressure in eyes with irregular corneas. METHODS: GAT and DCT measures were taken in 30 keratoconus and 29 postkeratoplasty eyes of 35 patients after pachymetry and corneal topography. Regression and correlation analyses were performed between both tonometry methods and between tonometry methods and corneal parameters. Bland-Altman plots were constructed. RESULTS: DCT values were significantly higher than GAT values in both study groups: +4.1 +/- 2.3 mm Hg (mean +/- SD) in keratoconus and +3.1 +/- 2.5 mm Hg after keratoplasty. In contrast to DCT, GAT values were significantly higher in postkeratoplasty eyes than in keratoconus. The correlation between the 2 tonometry methods was moderate in keratoconus (Kendall correlation coefficient, tau = 0.34) as well in postkeratoplasty eyes (tau = 0.66). The +/-1.96 SD span of the DCT-GAT differences showed a considerable range: -0.42 to +8.70 mm Hg in keratoconus and -1.87 to +7.98 mm Hg in postkeratoplasty eyes. In the keratoconus group, neither DCT nor GAT correlated significantly with any of the corneal parameters. In the postkeratoplasty group, both DCT and GAT measures showed a moderate positive correlation with corneal steepness, but only DCT had a significant negative correlation with the central corneal thickness (tau = -0.33). CONCLUSIONS: DCT measured significantly higher intraocular pressures than GAT in keratoconus and postkeratoplasty eyes. DCT and GAT measures varied considerably, and DCT was not less dependent on biomechanical properties of irregular corneas than GAT.

Novel pressure-to-cornea index in glaucoma.

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Visual function in human ocular toxoplasmosis.

AIM: To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis. METHODS: 61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (> or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual field damage was correspondingly graded as mild (mean defect <4 dB), moderate (mean defect 4-12 dB) or severe (mean defect >12 dB). RESULTS: 8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p<0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity. CONCLUSION: In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in >94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.

Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma.

PURPOSE: To describe a case series of neovascular glaucoma (NVG) caused by central retinal vein occlusion (CRVO) that was treated with intravitreal bevacizumab (IVB; Avastin). DESIGN: Retrospective interventional case series. METHODS: Six consecutive patients with NVG and a refractory, symptomatic elevation of intraocular pressure (IOP) and pronounced anterior segment congestion received IVB (1.25 mg/0.05 ml). Diode laser cyclophotocoagulation was carried out only if pressure was controlled insufficiently by topical medication. Follow-up examinations occurred at four to 16 weeks. RESULTS: IVB resulted in a marked regression of anterior segment neovascularization and relief of symptoms within 48 hours. IOP decreased substantially in three eyes; in the other three eyes, adjuvant cyclophotocoagulation was necessary. No side effects were observed. Panretinal photocoagulation (PRP) was performed as soon as feasible, five to 12 weeks after IVB treatment. CONCLUSION: IVB leads to a rapid regression of iris and angle neovascularization and should be investigated more thoroughly as an adjunct in the management of NVG.

In vivo pachymetry in normal eyes of rats, mice and rabbits with the optical low coherence reflectometer.

The aim of this study was to determine the central corneal thickness (CCT) in living rats, mice and rabbits using a non-contact, high-speed optical low coherence reflectometer (OLCR) mounted on a regular slit lamp. Both eyes of eight male Wistar rats, eight male balb-c mice and eight male Japanese rabbits were measured. Each eye was measured twice (one measurement consists of 20 scans), the average calculated. Additionally, CCT was measured in rabbits using an ultrasound pachymeter. The mean CCT was: RATS: 159.08 microm (SD+/-14.99 microm), MICE: 106.0 microm (SD+/-3.45 microm) and RABBITS: 356.11 microm (SD+/-14.34 microm). With the use of OLCR we were able to accurately measure the CCT of rats, mice and rabbits in vivo. This technique may prove useful in further refractive, pharmacological and glaucoma studies.