Noelia García

Reproducibility and Clinical Relevance of the Ocular Response Analyzer in Nonoperated Eyes: Corneal Biomechanical and Tonometric Implications

PURPOSE To assess the reproducibility of the ocular response analyzer (ORA) in nonoperated eyes and the impact of corneal biomechanical properties on intraocular pressure (IOP) measurements in normal and glaucomatous eyes. METHODS In the reliability study, two independent examiners obtained repeated ORA measurements in 30 eyes. In the clinical study, the examiners analyzed ORA and IOP-Goldmann values from 220 normal and 42 glaucomatous eyes. In both studies, Goldmann-correlated IOP measurement (IOP-ORAg), corneal-compensated IOP (IOP-ORAc), corneal hysteresis (CH), and corneal resistance factor (CRF) were evaluated. IOP differences of 3 mm Hg or greater between the IOP-ORAc and IOP-ORAg were considered outcome significant. RESULTS Intraexaminer intraclass correlation coefficients and interexaminer concordance correlation coefficients ranged from 0.78 to 0.93 and from 0.81 to 0.93, respectively, for all parameters. CH reproducibility was highest, and the IOP-ORAg readings were lowest. The median IOP was 16 mm Hg with the Goldmann tonometer, 14.5 mm Hg with IOP-ORAg (P < 0.001), and 15.7 mm Hg with IOP-ORAc (P < 0.001). Outcome-significant results were found in 77 eyes (29.38%). The IOP-ORAc, CH, and CRF were correlated with age (r = 0.22, P = 0.001; r = -0.23, P = 0.001; r = -0.14, P = 0.02, respectively), but not the IOP-ORAg or IOP-Goldmann. CONCLUSIONS The ORA provides reproducible corneal biomechanical and IOP measurements in nonoperated eyes. Considering the effect of ORA, corneal biomechanical metrics produces an outcome-significant IOP adjustment in at least one quarter of glaucomatous and normal eyes undergoing noncontact tonometry. Corneal viscoelasticity (CH) and resistance (CRF) appear to decrease minimally with increasing age in healthy adults.

Cirrus High-Definition Optical Coherence Tomography Compared with Stratus Optical Coherence Tomography in Glaucoma Diagnosis

PURPOSE To compare the retinal nerve fiber layer (RNFL) evaluation using Cirrus optical coherence tomography (OCT) and Stratus OCT in glaucoma diagnosis. METHODS One hundred thirty normal and 86 patients with glaucoma were included in this prospective study. The signal strengths of the OCTs were evaluated. The sensitivities and specificities of global RNFL average thickness were compared in the four quadrants and in each clock hour sector. Receiver operating characteristic (ROC) curves, areas under the ROC (AUC), and the likelihood ratio (LR) were plotted for RNFL thickness. Agreement between the OCTs was calculated by using the Bland-Altman method and kappa (kappa) coefficient. RESULTS Twenty-three percent of all cases examined with Stratus OCT and 1.9% examined with Cirrus OCT had a signal strength below 6 (P = 0.01). In cases with signal strengths > or =6, the mean signal strength was higher with Cirrus OCT than with Stratus OCT (P = 0.01). The RNFL measurements by Cirrus were thicker than those of Stratus OCT (P < 0.05). The AUCs were 0.829 for Stratus and 0.837 for Cirrus OCT (P = 0.706) for global RNFL average. LRs were similar in both OCTs in global RNFL classification but varied in quadrants. The widths of the limits of agreement varied between 42.16 and 97.79 microm. There was almost perfect agreement (kappa = 0.82) in the average RNFL classification. CONCLUSIONS Cirrus OCT has better scan quality than Stratus OCT, especially in glaucomatous eyes. In cases with good-quality scans, the sensitivity and specificity, and AUCs were similar. The best agreement was in the global average RNFL classification. The widths of limits of agreements exceed the limits of resolution of the OCTs.

Comparison of retinal nerve fiber layer thickness values using Stratus Optical Coherence Tomography and Heidelberg Retina Tomograph-III.

PurposeTo evaluate the usefulness of retinal nerve fiber layer (RNFL) thickness measurements using the Heidelberg Retina Tomograph-III (HRT-III) in normal, ocular hypertensive, and glaucomatous eyes and compare the thickness measurements using HRT-III and Stratus Optical Coherence Tomography-3 (OCT-3). MethodsSixty-nine normal eyes, 60 eyes ocular hypertensive, and 111 glaucomatous were included. All participants underwent visual field, HRT-III, and OCT-3 examinations on the same day. Patients were classified into 3 groups according to intraocular pressure and visual field damage. The sensitivity/specificity of RNFL thickness measurements and RNFL thickness classifications using HRT-III and OCT-3 were calculated. The sensitivity/specificity of the height variation contour (HVC) from the HRT-III were calculated. The receiver operating characteristic curves (ROC) and areas under the ROC were plotted. Agreement was calculated using Bland-Altman method and the κ coefficient. ResultsThe RNFL thickness sensitivity/specificity were 32.4%/87%, for the HRT-III and 72.97%/81.15% for the OCT-3 in relation to the glaucoma diagnosis (least specific criteria). The RNFL thickness sensitivities/specificities were lower in early glaucoma. The areas under the ROC for RNFL measurements were 0.72 using HRT-III, 0.86 with OCT-3 (P=0.001), and 0.54 for the HVC. The RNFL classification κ coefficient was 0.36. Bland-Altman analysis confirmed that the RNFL measurements were not interchangeable. ConclusionsThe sensitivity of RNFL damage detection using HRT-III was lower compared with OCT-3, especially in early glaucoma. RNFL thickness agreement between HRT-III and OCT-3 was only fair. HVC was not useful for glaucoma detection.

Rebound tonometer compared with goldmann tonometer in normal and pathologic corneas.

Purpose: To compare the intraocular pressure (IOP) measurements obtained with the rebound tonometer (RT) and the Goldmann handheld tonometer (GT) in normal and altered corneas. Methods: A total of 208 normal corneas and 50 corneas with pathologies were included in this prospective study. All measurements were randomly obtained by 1 observer. The medians and interquartile range (IR) for both tonometers were compared. The median differences were assessed in IOP groups. Agreement between the tonometers was calculated using the Bland-Altman method. Results: The median IOP in all eyes was 17 mm Hg (IR, 13-22 mm Hg) with the RT and 16 mm Hg (IR, 13-21 mm Hg) with the GT (P < 0.001). The correlation was excellent between tonometers (r2 = 0.86; P < 0.001). The minimal differences between the two were obtained from 10 to 20 mm Hg (GT). The Bland-Altman scatterplot obtained good agreement between the instruments. In normal corneas, the median difference was ≤2 mm Hg in 77.4% of cases. In the altered corneas, the median difference was ≤2 mm Hg in 73% of cases (P = 0.21 compared with the normal group). In 10% and 2% of cases, the IOP could not be measured using the GT and RT, respectively. Conclusions: The results were similar for both tonometers. In the altered corneas, the IOP could be difficult to obtain with the GT because of distorted half-circles. The 1-mm-diameter disposable RT tip facilitated obtaining measurements without anesthetic drops, which avoids infections. The RT could be useful in routine clinical settings when measuring IOP in corneas with pathologies.

Intra- and inter-day variation of cytokines and chemokines in tears of healthy subjects

Tear levels of certain cytokines/chemokines can potentially serve as biomarkers for dry eye and other ocular surface diseases if they remain stable from day-to-day in healthy eyes. The aim of this study was to determine the normal intra- and inter-day variation of selected tear cytokines/chemokines. Tear samples from 24 young, healthy adults were collected 11:00 AM-1:00 PM (mid-day) and 5:00-7:00 PM (evening) on three non-consecutive days. Concentrations of 18 cytokines/chemokines (EGF, eotaxin, CX3CL1/fractalkine, GM-CSF, IFN-γ, IL-10, IL-1β, IL-13, IL-17A, IL-1RA, IL-5, IL-6, CXCL8/IL-8, IL-9, CXCL10/IP-10, CCL5/RANTES, TNF-α, and VEGF) were measured by multiplex bead analysis. Ocular surface disease was ruled out by clinical tests. A random-effects ANOVA model was used to evaluate intra- and inter-day effects on cytokine/chemokine levels. Repeatability of intra-subject inter-day measurements was assayed by coefficient of variation. Ten out of the 18 molecules had detectable tear levels in >50% of the subjects. Of those, only IL-10 and IL-1β levels had significant inter-day variations. EGF, CX3CL1/fractalkine, CXCL10/IP-10, and VEGF were consistently higher in the evening compared to the mid-day measurements. EGF, CXCL10/IP-10, VEGF and CXCL8/IL-8had good intra-subject reproducibility. In conclusion, tear cytokines/chemokines can be measured reproducibly over time, with most not having significant inter-day variability. Some varied significantly depending upon the time of tear collection, and these variations should be taken into account when comparisons are made. The good intra-subject reproducibility for EGF, CXCL10/IP-10, CXCL8/IL-8, and VEGF indicates that these molecules could potentially serve as biomarkers of ocular surface disease.

Basal values, intra-day and inter-day variations in tear film osmolarity and tear fluorescein clearance

Abstract Purpose: The aim of this study was to determine the normal inter-day and intra-day variations in tear film osmolarity and the tear fluorescein clearance test (T-FCT) in healthy subjects. Methods: Tear samples from 24 young, healthy adults were collected from 11:00 AM to 1:00 PM (midday) and 5:00 PM to 7:00 PM (evening) on three non-consecutive days. Tear osmolarity measurement and the T-FCT were performed to assess the basal values and inter-day and intra-day variations of the test results. A freezing point depression osmometer was used to analyze the tear osmolarity, and the T-FCT was performed using a fluorophotometer. Results: The mean osmolarity value was 270 ± 4.4 mOsm/l and the mean T-FCT result was 2.97 ± 0.17 fluorescence arbitrary units. The inter-day or intra-day tear osmolarity values did not differ significantly. The T-FCT results varied significantly during the day, with significantly (p = 0.0004) higher results in the evening; no significant differences were found in the inter-day analysis. Conclusions: Tear osmolarity was unaffected by intra-day variations; however, the T-FCT showed an inter-day variation, which indicated that the time of day when the test is performed must be considered when it is used to evaluate the diagnosis of dry eye disease, disease progression or therapeutic effectiveness.

Influence of examiner experience on the reproducibility of retinal nerve fiber thickness values using Cirrus and Stratus OCTs.

Purpose:The purpose of the study was to evaluate the influence of the examiner’s experience on the reproducibility of retinal nerve fiber layer (RNFL) measurements obtained with Cirrus optical coherence tomography (OCT) and Stratus. Methods:Fifty-one normal and glaucomatous eyes of 51 participants were included. Two examiners (1 novice, 1 experienced) obtained 2 scans using both OCTs. For quantitative measurements, Bland and Altman limits of agreement were evaluated. For qualitative classifications, &kgr; coefficients were calculated. Results:Signal strength was higher with Cirrus than with Stratus (P<0.05). Signal strength was higher in scans performed by the experienced examiner than in those carried out by the inexperienced examiner in Stratus but not in Cirrus. RNFL measurement differences between Cirrus and Stratus were influenced by the examiner for the inferior (P=0.02), superior (P<0.001), and temporal quadrants (P=0.009). The RNFL quantitative agreement of examiners was higher in Cirrus than in Stratus. The qualitative agreement (&kgr; coefficients) of both examiners in the RNFL classification were almost perfect with Cirrus (in the average, superior, and inferior quadrants), and moderate with Stratus (only in average and inferior quadrant). Conclusions:The signal strength is independent of the examiner’s experience in Cirrus but not in Stratus. RNFL measurements obtained by both examiners were more reproducible with Cirrus than with Stratus. The differences in RNFL measurements between both OCTs were related to the examiner’s experience in all 3 quadrants. Agreement between operators in the RNFL classification was higher with Cirrus than Stratus.

Lack of Agreement among Electrical Impedance and Freezing-Point Osmometers.

Purpose To assess the interchangeability of tear osmolarity measurements between electrical impedance and freezing-point depression osmometers and to analyze inter-eye tear osmolarity variability measured with these osmometers in healthy subjects. Methods Tear osmolarity was measured using the TearLab osmometer (OcuSense Inc., San Diego, CA) and the Fiske 210 microsample osmometer (Advanced Instruments Inc., Norwood, MA). We randomly selected one eye in 50 subjects (29 women, 21 men; mean age, 33.16 ± 6.11 years) to analyze whether osmolarity measurements by these osmometers were interchangeable. Both eyes of 25 patients (15 women, 10 men; mean age, 34.32 ± 6.37 years) were included to analyze inter-eye osmolarity variability. Results The mean tear osmolarity values measured with the TearLab osmometer were higher (305.22 ± 16.06 mOsm/L) than those with the Fiske 210 osmometer (293.40 ± 12.22 mOsm/L), with the intraclass correlation coefficient being 0.23 (p = 0.051). A Bland-Altman plot showed that the systems were not interchangeable because there was a systematic difference, with the limits of agreement being −17.93 to 41.57 mOsm/L. There were no statistically significant differences (p = 0.5006 and p = 0.6533, respectively) between an individual’s eyes measured with either osmometer. Conclusions Because the TearLab tear osmolarity measurements were higher than those of the Fiske 210 measurements and the limits of agreement were too wide, the two osmolarity values cannot be used interchangeably. In healthy subjects, there is no difference in tear osmolarity between right and left eyes of the same individual measured with both instruments.