Morphological characteristics of eyes with neovascular age-related macular degeneration and good long-term visual outcomes after anti-VEGF therapy.

PURPOSE: To analyse the morphological characteristics of eyes with neovascular age-related macular degeneration (AMD) with good long-term visual acuity after anti-VEGF (vascular endothelial growth factor) therapy. METHODS: Retrospective, observational study of 175 patients with neovascular AMD with >5 years of follow-up after initiating anti-VEGF therapy. Spectral-domain optical coherence tomography images were assessed for thickness of pigment epithelial detachment (PED), subretinal hyper-reflective material (SHRM), subretinal fluid and subfoveal choroidal, as well as the integrity of the outer retinal bands. RESULTS: The final analysis cohort included 203 eyes (175 patients) followed for a mean of 7.84±1.70 years (range: 5-11). The maximum PED thickness in the foveal central subfield (FCS) was significantly lower (p<0.001) in the poor vision group (13.11 µm) compared with the intermediate (86.25 µm) or good (97.92 µm) vision groups, respectively. In contrast, the maximum thickness of SHRM in the FCS was significantly thicker (p<0.001) in eyes with poor vision (149.46 µm) compared with eyes with intermediate vision (64.37 µm) which in turn were significantly thicker (p<0.001) than eyes with good vision (9.35 µm). The good vision group also had better continuity of all outer retinal bands (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) compared with the other two groups (all p<0.001). CONCLUSION: A thicker PED and thinner SHRM were correlated with better vision in eyes with neovascular AMD following long-term anti-VEGF therapy. If replicated in future prospective studies, these findings may have implications for design of optimal anatomic endpoints for neovascular AMD treatment.

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study.

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials.

Peripheral extent of the choroidal circulation by ultra-widefield indocyanine green angiography in healthy eyes.

AIM: To analyse the peripheral extent of choroidal circulation using ultra-widefield (UWF) indocyanine green angiography (ICGA) in healthy eyes. METHODS: UWF ICGA images of 55 eyes of 36 healthy subjects were captured using the Optos California (Optos, Dunfermline, United Kingdom) in this prospective observational study. Images were analysed to locate the peripheral extent of the visible choroidal circulation, and the boundary was marked in ImageJ (v1.52). Each pixel annotated as the border of the choroidal circulation was projected individually to its anatomically correct location on the three-dimensional model eye, and spherical trigonometry was applied (using the Optos software) to calculate its respective radial distance from the centre of the optic disc in metric units (corrected by stereographic projection) for each quadrant. RESULTS: The mean area of the peripheral extent was estimated to be 893.2 mm2 (95% CI: 844.2 to 942.3 mm2). The mean distance (range) of this boundary from optic nerve centre was 18.22 mm (95% CI: 14.0 to 23.14 mm). Multiple regression analysis with age, gender, axial length or ethnicity showed no relationship. There was excellent inter-grader reproducibility, with intraclass correlation coefficients of 0.95 (95% CI: 0.80 to 0.99, p<0.001) for distance and 0.99 (95% CI: 0.988 to 0.999, p<0.001) for area measurements. CONCLUSIONS: The peripheral choroidal boundary may be defined using UWF ICGA. Knowledge of the normal extent and its variability is essential to understand the impact of disease on the choroidal vasculature.

Quantifying the Size of the Pterygium Head by Evaluating the Fibrous Area or the Vascularized Area.

PURPOSE: Pterygium is characterized by the development of wing-shaped fibrovascular tissue from the bulbar conjunctiva across the limbus onto the cornea. The purpose of this study was to quantify the discrepancy of the pterygium size between the fibrous area and the vascularized area. METHODS: Color photographs of 146 eyes with pterygia obtained with a single-lens reflex camera system were analyzed by 2 independent graders for width (vertical dimension), length (horizontal dimension), and surface area of the pterygium head using 2 methods: the fibrous method, which measures any fibrovascular tissue crossing the corneal limbus, and the vascular method, which measures only tissue with discernible active blood flow, without any avascular tissue or opacity. Statistics of intraclass correlation coefficients for intergrader and intragrader reproducibility were calculated, and the paired t test between methods was used. RESULTS: Both intergrader and intragrader intraclass correlation coefficients for both methods were above 0.85. The vascular measurement was significantly larger in width (vertical dimension, fibrous 3.97 ± 1.02 mm vs. vascular 4.49 ± 1.33 mm, P = 0.01), whereas the fibrous measurement was significantly larger in length (horizontal dimension, fibrous 2.41 ± 1.16 mm vs. vascular 2.23 ± 1.05 mm, P = 0.04). No significant difference was found in the surface area (fibrous 7.27 ± 4.65 mm vs. vascular 7.40 ± 5.13 mm, P = 0.67). CONCLUSIONS: With both methods, reproducibility of the size of the pterygium head was high. Significant differences were shown between the two methods in quantification of the width and length but not in the surface area. Such methods can be used to standardize the evaluation of pterygia in clinical research and clinical trials.

Reproducibility and agreement of four anterior segment-optical coherence tomography devices for anterior chamber angle measurements.

PURPOSE: To compare the reproducibility and agreement of anterior chamber angle (ACA) parameters and metrics obtained by four different anterior segment-optical coherence tomography (AS-OCT) devices. METHODS: In this prospective study, 30 eyes from 15 normal subjects underwent anterior segment angle scanning using the Spectralis, Cirrus, and Optovue spectral domain optical coherence tomography (SD-OCT), as well as the Visante time-domain optical coherence tomography (TD-OCT). For each eye, the scan line was performed perpendicularly on the inferior (270°) angle, and the inferior ACA image was acquired 2 times. Inter-instrument and intra-instrument, as well as inter-observer and intra-observer reproducibility of anterior chamber angle metrics, Schwalbe's line (SL) to scleral spur (SS) distance (TM-Span), angle opening distance (AOD), and trabecular iris space area (TISA) measurements, were evaluated by intraclass correlation coefficients (ICCs) and Bland-Altman plots with limits of agreement (LoA). RESULTS: For this cohort of 30 eyes of 15 normal subjects, the mean TM-Span, AOD, and TISA were 0.966 ± 0.198 mm, 0.750 ± 0.205 mm, and 0.286 ± 0.090 mm2 from the Spectralis; 0.929 ± 0.113 mm, 0.717 ± 0.120 mm, and 0.267 ± 0.095 mm2 from the Cirrus; 0.923 ± 0.191 mm, 0.683 ± 0.161 mm, and 0.265 ± 0.072 mm2 from the Optovue; and 0.970 ± 0.070 mm, 0.705 ± 0.150 mm, and 0.279 ± 0.065 mm2 from the Visante. The intra-instrument (ICCs > 0.838), intra-grader (ICCs > 0.910), and inter-grader (ICCs > 0.869) agreement were good. Agreement between the four instruments was also good with ICCs from 0.901 to 0.967 for TM-Span, 0.887 to 0.941 for AOD, and 0.923 to 0.961 for TISA. CONCLUSIONS: Consistent and reproducible ACA measurements could be obtained from multiple AS-OCT devices including both SD- and TD-OCT instruments. These findings have relevance when considering multiple imaging devices in future studies.

Distribution and Location of Vortex Vein Ampullae in Healthy Human Eyes as Assessed by Ultra-Widefield Indocyanine Green Angiography.

PURPOSE: To study the number and distribution of vortex ampullae in healthy eyes using ultra-wide field (UWF) indocyanine green angiography (ICGA). DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-six eyes of 36 healthy participants with no evidence of ocular or systemic disease. METHODS: The UWF ICGA images (central and peripheral steered) were captured using the Optos California (Optos, Dunfermline, United Kingdom) instrument. The images were projected stereographically to correct for peripheral distortion and obtain accurate measurements. All images were graded and analyzed for number, location, and distance of the vortex vein ampullae from the center of optic nerve. MAIN OUTCOME MEASURES: Mean number and the distance of ampullae from the center of optic nerve in all quadrants. RESULTS: The mean number of ampullae observed by UWF ICGA was 8.0±2.1 (range, 5-13). The mean distance of a vortex vein ampulla from the optic nerve was 14.2±1.1 mm (range, 10.3-17.7 mm). The frequency of ampullae was higher in the superior and inferior quadrants than the nasal and temporal quadrants. Ampullae were never observed in the 3- or 9-o'clock meridians. Multiple regression analysis showed no relationship with age, gender, axial length, or ethnicity. Excellent intergrader reproducibility was found between graders with an intraclass correlation coefficient (distance measurements: intraclass correlation coefficient, 0.99; 95% CI, 0.979-0.999; P < 0.001; number of ampullae: intraclass correlation coefficient, 0.99; 95% CI, 0.988-0.999; P < 0.001). CONCLUSIONS: The number of discrete vortex vein ampullae that can be discerned by UWF ICGA in healthy individuals is greater frequently and substantially than the 4 that are traditionally thought to drain the major quadrants. Considerable variability in the number and position of the ampullae may be apparent in healthy individuals.

Comparison of manual & automated analysis methods for corneal endothelial cell density measurements by specular microscopy / Comparación de los métodos de análisis manual y automatizado para medir la densidad celular endotelial corneal mediante microscopio especular

Purpose: To determine the reliability of corneal endothelial cell density (ECD) obtained by automated specular microscopy versus that of validated manual methods and factors that predict such reliability. Methods:Sharp central images from 94 control and 106 glaucomatous eyes were captured with Konan specular microscope NSP-9900. All images were analyzed by trained graders using Konan CellChek Software, employing the fully- and semi-automated methods as well as Center Method. Images with low cell count (input cells number <100) and/or guttata were compared with the Center and Flex-Center Methods. ECDs were compared and absolute error was used to assess variation. The effect on ECD of age, cell count, cell size, and cell size variation was evaluated. Results:No significant difference was observed between the Center and Flex-Center Methods in corneas with guttata (p = 0.48) or low ECD (p = 0.11). No difference (p = 0.32) was observed in ECD of normal controls < 40 yrs old between the fully-automated method and manual Center Method. However, in older controls and glaucomatous eyes, ECD was overestimated by the fully-automated method (p = 0.034) and semi-automated method (p = 0.025) as compared to manual method. Conclusion: Our findings show that automated analysis significantly overestimates ECD in the eyes with high polymegathism and/or large cell size, compared to the manual method. Therefore, we discourage reliance upon the fully-automated method alone to perform specular microscopy analysis, particularly if an accurate ECD value is imperative

Objetivo: Determinar la fiabilidad de la densidad celular endotelial corneal (ECD) obtenida mediante microscopio especular automático frente a métodos manuales validados y factores predictivos de la fiabilidad. Métodos: Se capturaron imágenes nítidas de 94 controles y 106 ojos glaucomatosos con un microscopio especular Konan NSP-9900. Todas las imágenes fueron analizadas por examinadores expertos mediante el software Konan CellChek, utilizando los métodos automatizado total, semiautomático y de centrado. Se compararon las imágenes con bajo recuento celular (número de células <100) y/o córnea guttata con el método de centrado y centrado flexible. Se compararon las ECD, utilizándose el error absoluto para valorar la variación. Se evaluó el efecto de la ECD sobre la edad, el recuento celular, el tamaño celular y la variación del tamaño celular. Resultados: No se observó diferencia significativa entre los métodos de centrado y centrado flexible en las córneas con guttata (p = 0,48) o baja ECD (p = 0,11). No se observó diferencia (p = 0,32) en cuanto a ECD en los controles normales < 40 años entre el método totalmente automatizado y el método de centrado manual. Sin embargo, en los controles mayores y en los ojos glaucomatosos, la ECD fue sobreestimada por el método totalmente automatizado (p = 0,034) y el método semiautomático (p = 0,025), en comparación al método manual. Conclusión: Nuestros hallazgos muestran que los análisis automatizados sobreestiman considerablemente la ECD en los ojos con alto polimegatismo y/o gran tamaño celular, en comparación al método manual. Por tanto, no recomendamos confiar en el método totalmente automatizado por sí solo para realizar estudios mediante microscopio especular, particularmente en casos en que la precisión del valor de ECD sea imperativo

Comparison of manual & automated analysis methods for corneal endothelial cell density measurements by specular microscopy.

PURPOSE: To determine the reliability of corneal endothelial cell density (ECD) obtained by automated specular microscopy versus that of validated manual methods and factors that predict such reliability. METHODS: Sharp central images from 94 control and 106 glaucomatous eyes were captured with Konan specular microscope NSP-9900. All images were analyzed by trained graders using Konan CellChek Software, employing the fully- and semi-automated methods as well as Center Method. Images with low cell count (input cells number <100) and/or guttata were compared with the Center and Flex-Center Methods. ECDs were compared and absolute error was used to assess variation. The effect on ECD of age, cell count, cell size, and cell size variation was evaluated. RESULTS: No significant difference was observed between the Center and Flex-Center Methods in corneas with guttata (p=0.48) or low ECD (p=0.11). No difference (p=0.32) was observed in ECD of normal controls <40 yrs old between the fully-automated method and manual Center Method. However, in older controls and glaucomatous eyes, ECD was overestimated by the fully-automated method (p=0.034) and semi-automated method (p=0.025) as compared to manual method. CONCLUSION: Our findings show that automated analysis significantly overestimates ECD in the eyes with high polymegathism and/or large cell size, compared to the manual method. Therefore, we discourage reliance upon the fully-automated method alone to perform specular microscopy analysis, particularly if an accurate ECD value is imperative.

Comparison of Noncontact Specular and Confocal Microscopy for Evaluation of Corneal Endothelium.

PURPOSE: To compare endothelial cell analysis obtained by noncontact specular and confocal microscopy, using the Konan NSP-9900 and Nidek ConfoScan4 systems, respectively. METHODS: Three groups including 70 healthy eyes, 49 eyes with Fuchs endothelial corneal dystrophy (FECD), and 78 eyes with glaucoma were examined with both the Konan NSP-9900 specular microscope and the Nidek ConfocScan4 confocal microscope. Certified graders at the Doheny Image Reading Center compared corneal endothelial images from both instruments side by side to assess image quality. Endothelial cell density (ECD) measurements were calculated and compared using three different modalities: (1) each instrument's fully automated analysis; (2) each instrument's semiautomatic analysis with grader input; and (3) manual grading methods by certified grader. RESULTS: All normal eyes yielded gradable endothelial images, and most but not all glaucomatous eyes yielded images with high enough image quality to allow grading. In addition, in corneas with severe FECD, poor image quality precluded ECD grading by specular microscopy in 20 eyes (40.8%) but in only 4 (8.2%) confocal images from the same eyes. For the gradable images, the ECD values obtained using the manual grading method from either device were comparable with no statistically significant difference (P>0.05) between specular and confocal devices. Machine-generated ECD values were significantly different from manual results, measuring greater in all cases with specular microscopy. Machine-generated ECD values from confocal microscopy also differed significantly from manual determinations, but not in a consistent direction. Semiautomatic methods for both instruments obtained clinically acceptable ECD values. CONCLUSIONS: Automatic machine-generated ECD measurements differed significantly from manual assessments of corneal endothelium by both specular and confocal microscopy, suggesting that automated results should be used with caution. But ECD values derived manually were comparable between the two devices in both normal and glaucomatous eyes, suggesting that manually graded images from the two instruments can be used interchangeably for reliable ECD measurements. Because of a higher proportion of gradable images, confocal microscopy may be superior to specular microscopy for ECD measurements in FECD.

Corneal, Conjunctival effects and blood flow changes related to silicone hydrogel lens wear and their correlations with end of day comfort.

PURPOSE: First, to examine how wearing high and low modulus lenses with two different base curves affected lens fit, and the corneal tissue and bulbar conjunctival vascular tissue (bulbar redness and blood velocity). Secondly, to quantify the associations between these baseline and outcome variables and the third purpose was to correlate these variables with end of day comfort. METHODS: Thirty participants wore higher (PureVision (PV) 8.3, 8.6) and lower (Acuvue Advance (AA) 8.3, 8.7) modulus silicone hydrogel lenses for two weeks on a daily wear basis. Lens fitting characteristics were examined. Corneal epithelial thickness was measured and the cornea and conjunctiva were assessed. RBC velocity was estimated from high magnification bulbar conjunctival images. Subjective comfort/dryness was reported by participants using visual analogue scales. RESULTS: AA lenses were rated the most comfortable (ANOVA, p=0.041). The least movement was while using the AA 8.3 base curve lens (Tukey p=0.028). Steep AA and PV lenses showed significantly higher conjunctival staining at the 2 week visit (ANOVA, p=0.029). There was a significant decrease in RBC velocity with both steeper AA lenses vs PV lenses (Tukey, p=0.001). Comparing baseline and 2 week visits, there was a significant negative correlation for the PV 8.3 between comfort and superior bulbar staining (r=-0.53). For both the PV 8.3 and AA 8.3 reduced RBC velocity was correlated with dryness (r=0.61 and r=0.91, respectively). CONCLUSIONS: Physical differences in contact lenses affect structural and vascular functional aspects of the ocular surface and these may be associated with symptoms of dryness.

Validity of a new comprehensive pterygia grading scale for use in clinical research and clinical trial.

PURPOSE: To determine the reliability and agreement of a new comprehensive pterygium grading scale for use in clinical research and clinical trials. METHODS: Thirty eyes with pterygia were enrolled in this study. Primary gaze position and lateral gaze position images were taken of each eye with a modified single-lens reflex camera system. Our grading scale includes five parameters: two hyperemia parameters of pterygia on two different gaze position images and three size parameters, quantifying length, width, and area of the cornea encroachment of pterygium, using ImageJ software. All images were graded on the five parameters by two masked, certified reading center graders. Two graders independently graded all the images to determine inter-grader reliability. One grader regraded the images after 3 days to determine intra-grader reliability. Intraclass correlation coefficient (ICC) and inter-rater agreement statistic (κ) calculations were performed. RESULTS: The intra-grader reliability for hyperemia grading was high on both primary and lateral gazing positions (κ value is 0.93 and 0.96). The inter-grader reliability for hyperemia grading was also good (κ value is 0.85 and 0.87). The mean value of width, length, and area of the cornea encroachment of pterygium was 4.31 ± 2.04 mm, 2.08 ± 1.43 mm, and 7.84 ± 7.62 mm2, respectively. The intra-grader agreement on width, length, and area were excellent, with ICCs of 0.98 (95% CI 0.96-0.99), 0.99 (95% CI 0.98-1.0), and 0.97 (95% CI 0.94-0.99), respectively. The inter-grader agreement on width, length, and area were also excellent, with ICCs of 0.96 (95% CI 0.90-0.98), 0.99 (95% CI 0.98-0.99), and 0.99 (95% CI 0.97-0.99), respectively. CONCLUSIONS: There was excellent intra- and inter-observer reproducibility with the new comprehensive grading scale. This scale could lead to the development of standardized grading assessments and quantification of pterygia that would be valid in clinical research and clinical trials.

Corneal features in ocular graft-versus-host disease by in vivo confocal microscopy.

PURPOSE: The purpose of our study was to determine the morphological features of the corneal epithelial layers, sub-basal nerve plexus and anterior stroma in patients with ocular graft-versus-host disease (oGVHD) compared to non-GVHD dry eyes and normal controls, using in vivo confocal microscopy (IVCM). METHODS: IVCM was used to capture central cornea images from eight volunteers with normal healthy eyes, ten patients with non-GVHD dry eye syndrome (DES) and 15 patients with clinically diagnosed oGVHD, in a cross-sectional study. Morphological changes of the corneal epithelial layers and anterior stroma, characteristics of corneal nerves and presence of dendritic cells (DCs) were then evaluated. RESULTS: IVCM images obtained from 66 eyes were analyzed. The density of superficial epithelial cells was 636.07 ± 101.05 cells/mm2 in the oGVHD group, 827 ± 99.62 cells/mm2 in the DES group and 1277.2 ± 121.42 cells/mm2 in the control group (P < 0.001). The density of wing cells was 4499.79 ± 976.36 cells/mm2 in the oGVHD group, 4662.85 ± 319.72 cells/mm2 in DES group and 6556.38 ± 503.99 cells/mm2 in the control group (p < 0.001). The density of basal cells was 7850.93 ± 723.51 cells/mm2 in the oGVHD group, 8570 ± 913.32 cells/mm2 in DES group and 9759.8 ± 251.99 cells/mm2 in the control group (p < 0.01). The density of nerve fibers was 11.22 ± 5.46 mm/mm2 in the oGVHD group, 14.50 ± 4.27 mm/mm2 in DES group and 19.56 ± 4.75 mm/mm2 in the control group (p < 0.01). The DC density was 67.88 ± 71.82 cells/mm2 in the oGVHD group, 40.06 ± 31.95 cells/mm2 in the DES group and 29.45 ± 8.1 cells/mm2 in the control group (P > 0.05). Visible networks of activated keratocytes were seen in the anterior stroma of eyes with oGVHD and DES, but not in normal controls. CONCLUSIONS: IVCM revealed distinct microstructural changes in the corneas of patients with oGVHD and DES, similar between the two groups. Our findings suggest implications for use of IVCM to evaluate and monitor patients with dry eyes associated or not with GVHD.

Evaluating ocular blood flow.

Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography.

Effect of Angle of Incidence on Anterior Chamber Angle Metrics From Optical Coherence Tomography.

PURPOSE: To evaluate the local variability of anterior chamber angle (ACA) metrics obtained by time domain (TD) and spectral domain (SD) optical coherence tomography (OCT). MATERIALS AND METHODS: Anterior-segment OCT imaging was performed on 30 normal eyes using Visante TD-OCT and 40 normal eyes using Cirrus SD-OCT. For Visante OCT, a single 16-mm line scan of the inferior angle with 3 slightly different rotations of 265, 270, and 275 degrees was performed. For Cirrus OCT, a 5-line raster of the inferior angle was performed, centering the third scan line at the 6 o'clock position, with 0.25 mm between lines. ACA measurements were taken for angle-opening distance (AOD) and trabecular iris space area (TISA) at 500/750 µm from the scleral spur for Visante OCT and at Schwalbe's line (SL) for Cirrus OCT. RESULTS: For Visante OCT, AOD500 was 0.406 mm (SD=0.143 mm) and TISA500 was 0.139 mm (0.054 mm). There was no difference in AOD500, AOD750, TISA500, or TISA750 between the 3 scan orientations (P>0.1 for all comparisons). For Cirrus OCT, AOD500 was 0.850±0.318 mm and TISA500 was 0.325±0.145 mm. No difference was found in SL-AOD and SL-TISA between the 3 scan positions. CONCLUSIONS: These findings suggest that small local changes in the position of the OCT line scan spaced up to 1.0 mm apart on Cirrus, or 10-degree apart on Visante, did not significantly alter the inferior ACA metrics in achieving reliable measurements in young healthy eyes. Given the absence of tracking and registration for current anterior-segment OCT instruments, this observation is of relevance for longitudinal and dynamic studies of angle geometry.

Reproducibility and Agreement Between 2 Spectral Domain Optical Coherence Tomography Devices for Anterior Chamber Angle Measurements.

PURPOSE: To compare anterior chamber angle parameters based on the location of Schwalbe line (SL) from 2 spectral domain optical coherence tomography (SD-OCT) instruments and to measure their reproducibility. METHODS: Forty-two eyes from 21 normal, healthy participants underwent imaging of the inferior irido-corneal angle with the Spectralis and Cirrus SD-OCT under tightly controlled low-light conditions. SL-angle opening distance (SL-AOD) and SL-trabecular iris space area (SL-TISA) were measured by masked, certified graders at the Doheny Imaging Reading Center using customized grading software. Interinstrument and intrainstrument, as well as interobserver and intraobserver reproducibility of SL-AOD and SL-TISA measurements were evaluated by intraclass correlation coefficients (ICCs) and Bland-Altman plots with limits of agreement (LoA). RESULTS: The mean SL-AOD was 0.662±0.191 mm in Spectralis and 0.677±0.213 mm in Cirrus. The mean SL-TISA was 0.250±0.073 mm in Spectralis and 0.256±0.082 mm in Cirrus. The agreement for intrainstrument (ICCs>0.979), intragrader (ICCs>0.992), and intergrader (ICCs>0.929) was excellent. Excellent agreement between the 2 devices was also documented with a mean difference of -0.016 (LoA -0.125 to 0.092) mm for SL-AOD and -0.007 (LoA -0.056 to 0.043) mm in SL-TISA. CONCLUSIONS: Both SD-OCTs provided comparable measurements and permitted calculation of SL-based angle metrics. There was excellent interinstrument and intrainstrument and intraobserver and interobserver reproducibility for Spectralis and Cirrus SD-OCTs, suggesting true interchangeability between SD-OCT devices. This has the potential to lead to development of standardized grading assessments and quantification of angle parameters that would be valid across various SD-OCT devices.

Optical edge effects create conjunctival indentation thickness artefacts.

PURPOSE: Conjunctival compression observed in ultrahigh resolution optical coherence tomography (UHR-OCT) images of contact lens edges could be actual tissue alteration, may be an optical artefact arising from the difference between the refractive indexes of the lens material and the conjunctival tissue, or could be a combination of the two. The purpose of this study is to image the artefact with contact lenses on a non-biological (non-indentable) medium and to determine the origins of the observed conjunctival compression. METHODS: Two-dimensional cross-sectional images of the edges of a selection of marketed silicone hydrogel and hydrogel lenses (refractive index ranging from 1.40 to 1.43) were acquired with a research grade UHR-OCT system. The lenses were placed on three continuous surfaces, a glass sphere (refractive index n = 1.52), a rigid contact lens (n = 1.376) and the cornea of a healthy human subject (average n = 1.376). The displacement observed was analysed using ImageJ. RESULTS: The observed optical displacement ranged between 5.39(0.06) µm with Acuvue Advance and 11.99(0.18) µm with Air Optix Night & Day when the lens was imaged on the glass reference sphere. Similarly, on a rigid contact lens displacement ranged between 5.51(0.03) and 9.72(0.12) µm. Displacement was also observed when the lenses were imaged on the human conjunctiva and ranged from 6.49(0.80) µm for the 1-day Acuvue Moist to 17.4(0.22) µm for the Pure Vision contact lens. CONCLUSIONS: An optical displacement artefact was observed when imaging a contact lens on two rigid continuous surfaces with UHR-OCT where compression or indentation of the surface could not have been a factor. Contact lenses imaged in situ also exhibited displacement at the intersection of the contact lens edge and the conjunctiva, likely a manifestation of both the artefact and compression of the conjunctiva.

Reproducibility of anterior segment angle metrics measurements derived from Cirrus spectral domain optical coherence tomography.

PURPOSE: To investigate the reproducibility of anterior segment angle (ACA) metrics measurements in normal subjects on Cirrus spectral domain optical coherence tomography (SD-OCT). METHODS: 40 eyes from 20 healthy, normal subjects underwent anterior segment imaging using a Cirrus SD-OCT. For each eye, 2 acquisitions of 5-line raster scans were performed perpendicularly on the inferior (270 degrees) angle. The Schwalbe's line-angle opening distance (SL-AOD) and Schwalbe's line-trabecular-iris space area (SL-TISA) measurements were performed by masked certified reading center graders using customized grading software. Intra-acquisition, intergrader, and intragrader reproducibility of SL-AOD and SL-TISA measurements were evaluated by intraclass correlation coefficients (ICC), Bland-Altman plots, and computation of mean percent difference (MPD) and coefficient of variability (CV). RESULTS: The mean SL-AOD (average of 2 acquisitions) was 0.75 mm (range, 0.32 mm to 1.39 mm); SL-TISA was 0.28 mm² (range, 0.082 mm² to 0.569 mm²). The repeatability of Cirrus SD-OCT was excellent for both SL-AOD (MPD 4.74%, CV=0.92, ICC=0.99) and SL-TISA (MPD 9.4%, CV=0.8, ICC=0.99). The intragrader reproducibility was high for SL-AOD (MPD 4.28%, CV=0.94, ICC=0.995) and SL-TISA (MPD 6.05%, CV=0.89, ICC=0.993). The inter-grader reproducibility was not as good but still excellent for both SL-AOD (MPD 15.47%, CV=0.95, ICC=0.94) and SL-TISA (MPD 19.43%, CV=0.99, ICC=0.93). Bland-Altman plots of all comparisons did not demonstrate any apparent bias, with similar repeatability at various SL-AOD and SL-TISA values. CONCLUSIONS: In our population of young healthy adults with normal eyes, there was excellent intra-acquisition, intragrader, and intergrader reproducibility for Schwalbe's line-based ACA metrics obtained from Cirrus SD-OCT images. These SD-OCT-derived measures may serve as reliable descriptors of angle morphometry for use in clinical trials and clinical practice.

Reproducibility of angle metrics using the time-domain anterior segment optical coherence tomography: intra-observer and inter-observer variability.

PURPOSE: To evaluate the reproducibility of anterior chamber angle measurements obtained by the Zeiss Visante anterior segment optical coherence tomography (AS-OCT). METHODS: Twenty eyes from 20 normal subjects with open anterior chamber angles were studied. The anterior chamber angle was imaged using the Visante AS-OCT. The angle-opening distance (AOD 500, AOD 750), trabercular iris space area (TISA 500, TISA 750) and scleral spur angle (SS angle) at the inferior angle location were measured. All the subjects underwent imaging in a darkened room (1 foot candles measured at the eye). Images were graded in a masked fashion by certified Doheny Image Reading Center graders. For intra-grader reproducibility assessments, images were re-graded by the same grader 1 week later after random sorting of images. For inter-grader assessments, a second masked grader independently reviewed the images. Intraclass correlation coefficients (ICC) were used to assess reproducibility. RESULTS: Inferior angle measurements of AOD (500, 750), TISA (500, 750) and SS angle for 20 normal eyes were calculated. The intra-observer ICC calculations showed excellent reproducibility for all measurements (AOD 500 = 0.95, AOD 750 = 0.97, TISA 500 = 0.93, TISA 750 = 0.94, SS = 0.96; p < 0.001 for all). The inter-observer ICC calculations showed lower reproducibility for all measurements (AOD 500 = 0.71, p < 0.001; AOD 750 = 0.82, p < 0.001; TISA 500 = 0.49, p = 0.08; TISA 750 = 0.61, p = 0.02; SS = 0.75). CONCLUSION: Determination of anterior chamber angle measurements was possible with the time-domain AS-OCT, but only modest inter-observer reproducibility was found even among experienced graders.

Metrics of the normal cornea: anterior segment imaging with the Visante OCT.

PURPOSE: The purpose of the study was to obtain anterior segment biometry for 40 normal eyes and to measure variables that may be useful to design large diameter gas permeable contact lenses that sit outside the region normally viewed by corneal topographers. Also, the distribution of these variables in the normal eye and how well they correlated to each other were determined. METHODS: This is a cross-sectional study, in which data were collected at a single study visit. Corneal topography and imaging of the anterior segment of the eye were performed using the Orbscan II and Visante OCT. The variables that were collected were horizontal K reading, central corneal/scleral sagittal depth at 15 mm chord, and nasal and temporal angles at the 15 mm chord using the built-in software measurement tools. RESULTS: The central horizontal K readings for the 40 eyes were 43 +/- 1.73 D (7.85 +/- 0.31 mm), with +/- 95% confidence interval (CI) of 38.7 (8.7 mm) and 46.6 D (7.24 mm). The mean corneal/scleral sagittal depth at the 15 mm chord was 3.74 +/- 0.19 mm and the range was 3.14 to 4.04 mm. The average nasal angle (which was not different from the temporal angle) at the 15 mm chord was 39.32 +/- 3.07 degrees and the +/- 95%CI was 33.7 and 45.5 degrees. The correlation coefficient comparing the K reading and the corneal/scleral sagittal depth showed the best correlation (0.58, p < 0.001). The corneal/scleral sagittal depth at 15 mm correlated less with the nasal angle (0.44, p = 0.004) and the weakest correlation was for the nasal angle at 15 mm with the horizontal readings (0.32, p = 0.046). CONCLUSION: The Visante OCT is a valuable tool for imaging the anterior segment of the eye. The Visante OCT is especially effective in providing the biometry of the peripheral cornea and sclera and may help in fitting GP lenses with a higher percentage of initial lens success, when the corneal sag and lens sag are better matched.