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Purpose To explore the correlation between longitudinal changes of peripapillary retinal nerve fiber layer (RNFL) thickness and the presence of parapapillary choroidal microvasculature dropout (MvD). Methods This is a longitudinal cohort study. All patients with normal-tension glaucoma (NTG) were recruited from the Wenzhou Glaucoma Progression Study. The presence of MvD was determined using optical coherence tomography (OCT) angiography and the RNFL thickness was evaluated by spectral-domain OCT. All assessments were performed both at baseline and at every 3-month follow-up for at least 18 months. Results Seventy-one eyes were included. The presence of MvD was observed in 23 NTG eyes (32.4%). Eyes with MvD had a thinner RNFL (68.8 ± 9.6 vs. 76.2 ± 16.7 μm, P = 0.016) and a faster rate of RNFL loss (-1.2 ± 1.5 vs. -0.4 ± 1.4 μm/y, P = 0.036) compared with those without MvD. In a univariate analysis of rates of RNFL loss, the presence of MvD at baseline (β = -0.83 ± 0.38, P = 0.033) was significantly associated with progressive RNFL loss. After adjusting for age, female sex, mean follow-up IOP, axial length, central corneal thickness, and mean deviation, the presence of MvD at baseline (β = -0.85 ± 0.41, P = 0.041) was significantly associated with faster rates of RNFL loss in the multivariate analysis. Conclusions There is a significant correlation between the presence of MvD and decrease in RNFL thickness in NTG patients. Our study further supported that the presence of MvD is a predictor of longitudinal RNFL damage in glaucoma.

To investigate regional alterations of macular microvasculature in primary open-angle glaucoma (POAG), and to determine the structure-function correlation between localized visual field defects and macular microvascular damage in matching sectors.Fifty-eight patients with POAG and 27 normal controls were recruited for this study. Optical coherence tomography angiography (OCTA) was used to measure retinal vascular microcirculation of the macula in superior, inferior, temporal, and nasal sectors. Visual field (VF) was tested using automated perimeter. Sensitivities of 16 central points of the VF were selected and divided into the 4 previously mentioned sectors. Structure-function correlation analysis was performed between localized visual field defects and the matching macular microvasculature damage. The relationship was also assessed using a previously described model.The temporal vascular density was thinner than those of the superior and inferior positions of parafovea in the control group (P 0.05). Vascular densities in all sectors were decreased in the POAG group compared with the normal control group (P 0.05). The structure-function correlation coefficients between sectors of VF sensitivity and the matched vascular densities ranged from 0.295 to 0.433 (P 0.01). The coefficient of determination between OCT derived vascular density measurements and the estimates using the previous model ranged from 0.08 to 0.19. The best fit was in the inferior sector.Compared with age-matched control subjects, vascular density of the parafoveal retina decreased in the POAG subjects. There is a moderate structure-function correlation between visual field sensitivity thresholds measured with automated perimeter and macular vascular density assessed by OCT.

Background Spectral domain optical coherence tomography (SD-OCT) was a useful tool to study accommodation in human eye, but the maximum image depth is limited due to the decreased signal-to-noise ratio (SNR). In this study, improving optical resolutions, speeds and the SNR were achieved by custom built SD-OCT, and the evaluation of the impact of the improvement during accommodation was investigated. Methods Three systems with different spectrometer designs, including two Charge Coupled Device (CCD) cameras and one Complementary Metal-Oxide-Semiconductor Transistor (CMOS) camera, were tested. We measured the point spread functions of a mirror at different positions to obtain the axial resolution and the SNR of three OCT systems powered with a light source with a 50 nm bandwidth, centered at a wavelength of 840 nm. Two normal subjects, aged 26 and 47, respectively, and one 75-year-old patient with an intraocular lens implanted were imaged. Results The results indicated that spectrometers using cameras with 4096 camera pixels optimized the axial resolutions, due to the use of the full spectrum provided by the light source. The CCD camera system with 4096 pixels had the highest SNR and the best image quality. The system with the CMOS camera with 4096 pixels had the highest speed but had a compromised SNR compared to the CCD camera with 4096 pixels. Conclusions Using these three OCT systems, we imaged the anterior segment of the human eye before and after accommodation, which showed similar results among the different systems. The system using the CMOS camera with an ultra-long scan depth, high resolution and high scan speed exhibited the best overall performance and therefore was recommended for imaging real-time accommodation.

Background To investigate thickness changes in the corneal epithelium and Bowman’s layer after overnight silicone hydrogel contact lens (CL) wear by using ultra-high resolution optical coherence tomography (UHROCT). Methods Eleven subjects without CL wearing history were recruited for this study. An UHROCT was used to measure the thickness of the epithelium (ET), Bowman’s layer (BT), stroma (ST), and total cornea (CCT) at the center of both eyes. A silicone hydrogel CL was inserted in the right eye of each subject, and the fellow non-CL wearing left eye served as the control. The lens was inserted at 9:30 pm and removed at 8:00 am the next morning. The subjects were evaluated at 9:00 pm (baseline), 9:30 pm (lens insertion), 10:00 pm (before sleep), 7:00 am (waking), 7:30 am, and 8:00 am (lens removal). Results Compared to the lens insertion level, the ET of the lens-wearing eye increased by 5.73% at eye opening (P = 0.001). The ET of the non-CL wearing eye and the BT in both eyes did not change after overnight CL wear. Compared to baseline, the CCT of the lens-wearing eye increased by 2.87% upon waking (P = 0.003) and recovered 30 min later (P = 0.555). In contrast, compared to baseline, the CCT of the non-CL wearing eye did not increase upon waking (P = 0.105). Conclusions By using UHROCT, we found that overnight CL wear induced different swelling responses in the various sublayers of the cornea. Trial registration Retrospectively registered. Registration number: ChiCTR1800015115. Registered 07 March 2018.

The goal was to determine the variability of the quantitative measurement of the bulbar conjunctival microvascular morphology and hemodynamics by testing the repeatability and variation during office hours. Functional slit-lamp biomicroscopy (FSLB) was used to image the bulbar conjunctival microvasculature, including the vessel diameter, blood flow velocity/rate and fractal dimensions of the microvascular network. The temporal side of the bulbar conjunctiva in 20 healthy subjects was imaged. The subject was imaged at 9 AM to test the measurement repeatability by two independent graders. The intraclass correlation coefficient (ICC) and coefficient of repeatability (CoR) were calculated. These same subjects were then imaged every two hours from 9 AM to 5 PM to test the variation during office hours. Custom software was used to semi-automatically process all measurements. The CoR% and ICC values between two graders for measuring the vessel diameter were 4.87% and 0.989, respectively. For the axial blood flow velocity, the CoR% and ICC were 11.49% and 0.997, respectively. From 9 AM to 5 PM, there were no significant variations in the vessel diameter and hemodynamics (P>0.05), whereas the fractal dimensions of the non-invasive microvascular perfusion maps (nMPMs) were significantly increased at 3 PM and 5 PM compared with the baseline obtained at 9 AM (P

Purpose To develop, test and validate functional slit lamp biomicroscopy (FSLB) for generating non-invasive bulbar conjunctival microvascular perfusion maps (nMPMs) and assessing morphometry and hemodynamics. Methods FSLB was adapted from a traditional slit-lamp microscope by attaching a digital camera to image the bulbar conjunctiva to create nMPMs and measure venular blood flow hemodynamics. High definition images with a large field of view were obtained on the temporal bulbar conjunctiva for creating nMPMs. A high imaging rate of 60 frames per second and an ~ 210 × high magnification were achieved using the camera inherited high speed setting and Movie Crop Function, for imaging hemodynamics. Custom software was developed to segment bulbar conjunctival nMPMs for further fractal analysis and quantitatively measure blood vessel diameter, blood flow velocity and flow rate. Six human subjects were imaged before and after 6 h of wearing contact lenses. Monofractal and multifractal analyses were performed to quantify fractality of the nMPMs. Results The mean bulbar conjunctival vessel diameter was 18.8 ± 2.7 μm at baseline and increased to 19.6 ± 2.4 μm after 6 h of lens wear (P = 0.020). The blood flow velocity was increased from 0.60 ± 0.12 mm/s to 0.88 ± 0.21 mm/s (P = 0.001). The blood flow rate was also increased from 129.8 ± 59.9 pl/s to 207.2 ± 81.3 pl/s (P = 0.001). Bulbar conjunctival nMPMs showed the intricate details of the bulbar conjunctival microvascular network. At baseline, fractal dimension was 1.63 ± 0.05 and 1.71 ± 0.03 analyzed by monofractal and multifractal analyses, respectively. Significant increases in fractal dimensions were found after 6 h of lens wear (P Conclusions Microvascular network's fractality, morphometry and hemodynamics of the human bulbar conjunctiva can be measured easily and reliably using FSLB. The alternations of the fractal dimensions, morphometry and hemodynamics during contact lens wear may indicate ocular microvascular responses to contact lens wear.

The retina provides a window to study the pathophysiology of cerebrovascular diseases. Pathological retinal microvascular changes may reflect microangiopathic processes in the brain. Recent advances in optical imaging techniques have enabled imaging of the retinal microvasculature at the capillary level, and the generation of high-resolution, non-invasive capillary perfusion maps (nCPMs) with the Retinal Function Imager (RFI). However, the lack of quantitative analyses of the nCPMs may limit the wider application of the method in clinical research. The goal of this project was to demonstrate the feasibility of automated segmentation and fractal analysis of nCPMs. We took two nCPMs of each subject in a group of 6 healthy volunteers and used our segmentation algorithm to do the automated segmentation for monofractal and multifractal analyses. The monofractal dimension was 1.885 ± 0.020, and the multifractal dimension was 1.876 ± 0.010 (P =0.108). The coefficient of repeatability was 0.070 for monofractal analysis and 0.026 for multifractal analysis. This study demonstrated that the automatic segmentation of nCPMs is feasible for fractal analyses. Both monofractal and multifractal analyses yielded similar results. The quantitative analyses of microvasculature at the capillary level may open up a new era for studying the microvascular diseases such as cerebral small vessel disease.

PURPOSE To test the feasibility of measuring the entire thickness profiles of the epithelium and contact lens (CL) in vivo, using high-speed and high-resolution spectral-domain optical coherence tomography (SD-OCT). METHODS A custom-built, long scan depth SD-OCT was developed based on a complementary metal oxide semiconductor (CMOS) camera, and the axial resolution was approximately 5.1 μm in tissue. Five eyes of five subjects were imaged twice across the horizontal meridian before and while wearing one CL. Semiautomatic measurement was done to yield the entire thickness profiles of the epithelium, total cornea, and CL after correcting for optical distortion. RESULTS The full width and depth of the epithelium, ocular surface, and CL were clearly visualized. The epithelial thickness at the center was 51.9±3.5 μm; it remained at this thickness across the central 7 mm diameter and then increased at both temporal and nasal peripheries. The CL profile showed the thinnest point at the center with thickness of 100.3±4.9 μm. The thickness increased toward the midperiphery and then decreased at the edge. CONCLUSIONS This pilot study demonstrated the feasibility of using high-speed CMOS-based OCT to evaluate the entire thickness profiles of the epithelium and CL in vivo. Further development will be needed to extend the scanning from 2D to 3D with a robust automatic image processing ability.

We demonstrated the feasibility of a CMOS-based spectral domain OCT (SD-OCT) for versatile ophthalmic applications of imaging the corneal epithelium, limbus, ocular surface, contact lens, crystalline lens, retina, and full eye in vivo. The system was based on a single spectrometer and an alternating reference arm with four mirrors. A galvanometer scanner was used to switch the reference beam among the four mirrors, depending on the imaging application. An axial resolution of 7.7 μm in air, a scan depth of up to 37.7 mm in air, and a scan speed of up to 70,000 A-lines per second were achieved. The approach has the capability to provide high-resolution imaging of the corneal epithelium, contact lens, ocular surface, and tear meniscus. Using two reference mirrors, the zero delay lines were alternatively placed on the front cornea or on the back lens. The entire ocular anterior segment was imaged by registering and overlapping the two images. The full eye through the pupil was measured when the reference arm was switched among the four reference mirrors. After mounting a 60 D lens in the sample arm, this SD-OCT was used to image the retina, including the macula and optical nerve head. This system demonstrates versatility and simplicity for multi-purpose ophthalmic applications.

To evaluate the resolutions of slit-lamp microscopy photography using various cameras.Evaluation of diagnostic test or technology.Healthy subjects were imaged with these adapted cameras through slit-lamp microscopy.A total of 8 cameras, including 6 custom-mounted slit-lamp cameras and 2 commercial slit-lamp cameras, were tested with standard slit-lamp microscopy devices for imaging of the eye. Various magnifications were used during imaging. A standard resolution test plate was used to test the resolutions at different magnifications. These outcomes were compared with commercial slit-lamp cameras.The main measurements included the display spatial resolutions, image spatial resolutions, and ocular resolutions. The outcome also includes the relationships between resolution and the pixel density of the displays and images.All cameras were successfully adapted to the slit-lamp microscopy, and high-quality ocular images were obtained. Differences in the display spatial resolutions were found among cameras [analysis of variance (ANOVA), P0.05]. Higher display resolutions were found with cameras using the high-definition multimedia interface (HDMI) compared with others, including cameras in smart phones. The display resolutions of smart phone displays were greater than cameras with video graphics array displays. The display spatial resolutions were found as a function of display pixel density (r0.95, P0.05) and magnification (r0.85, P0.05). Different image spatial resolutions were found among cameras (ANOVA, P0.05) as a function of image pixel density (r0.98, P0.05) and magnification (r0.85, P0.05). The commercial slitlamp with a single lens reflex camera yielded the highest image spatial resolution. However, the ocular resolution through binocular viewing of the slit-lamp microscopy was found to have the highest resolution compared with the display and image spatial resolutions of all of the cameras.Several cameras can be adapted with slit-lamp microscopy for ophthalmic imaging, yielding various display and image spatial resolutions. However, the resolution seemed to not be as good as ocular viewing through the slit-lamp biomicroscope.

The conjunctival and cerebral vasculatures share similar embryological origins, with similar structural and physiological characteristics. Tracking the conjunctival microvasculature may provide useful information for predicting the onset, progression and prognosis of both systemic and central nervous system (CNS) vascular diseases. The bulbar conjunctival vasculature was imaged using a retinal function imager (RFI, Optical Imaging Ltd, Rehovot, Israel). Hemoglobin in red blood cells was used as an intrinsic motion-contrast agent in the generation of detailed noninvasive capillary-perfusion maps (nCPMs) and the calculation of the blood flow velocity. Five healthy subjects were imaged under normal conditions and again under the stress condition of wearing a contact lens. The retina was also imaged in one eye of one subject for comparison. The nCPMs showed the conjunctival microvasculature in exquisite detail, which appeared as clear as the retinal nCPMs. The blood flow velocities in the temporal conjunctival microvasculature were 0.86 ± 0.08 (mean ± SD, mm/s) for the bare eye and 0.99 ± 0.11 mm/s with contact lens wear. It is feasible to use RFI for imaging the conjunctival vasculature.

PURPOSE: The aim of this study was to investigate the feasibility of automatic segmentation of the central corneal thickness (CCT) and epithelial thickness (ET) of the human cornea obtained with different spectral domain optical coherence tomography (OCT) instruments. METHODS: Ten left eyes from 10 healthy subjects with a mean age of 22.5 ± 1.5 years participated in this study. A custom-built ultra-high resolution OCT (UHR-OCT) with a 3-μm axial resolution, ultralong scan depth OCT (UL-OCT) with a 7.5-μm resolution, and commercial RTVue OCT with a 5-μm resolution were used to image the cornea. An automated segmentation algorithm was developed to process the OCT images and yield the CCT and ET. The measurement was verified by a manual measurement. RESULTS: The automatic algorithm successfully processed the central thickness of the cornea and corneal epithelium for all images. The average CCT obtained by the automatic segmentation algorithm was 528.1 ± 22.4 μm, 526.1 ± 23.4 μm, and 525.2 ± 23.7 μm for UHR-OCT, UL-OCT, and RTVue, respectively. The average ET was 53.2 ± 2.0 μm, 54.1 ± 3.0 μm, and 52.1 ± 2.5 μm for UHR-OCT, UL-OCT, and RTVue, respectively. These measurements were in agreement with those of the manual method for the CCT (all r>0.997, P 0.71, P

PURPOSE: To determine age-related changes of tear menisci in healthy subjects and to compare tear variables between age-matched normals and dry eye subjects. METHODS: Anterior segment optical coherence tomography was used to measure upper and lower tear menisci in healthy subjects (n = 197, 8-83 years) and in age-matched dry eye patients (n = 38, 19-72 years). Measured tear variables included the height and area of the tear meniscus. Tear meniscus volumes were calculated based on the cross-sectional areas of the tear menisci and the eyelid lengths. The age-related decrease rates of the tear menisci were also calculated. RESULTS: There were significant negative correlations between age and all tear meniscus dimensions (r ranged from -0.649 to -0.753; p < 0.05) in the healthy group. The rate of decrease for the total tear meniscus volume in healthy subjects was 1.0% per year. Compared with age-matched healthy subjects, the height, cross-sectional area, and volume of the upper and lower tear menisci in dry eye subjects were significantly smaller (p < 0.05). CONCLUSIONS: Tear menisci decreased with age in the healthy group. The variables in age-matched dry eye subjects were significantly lower than those in the healthy group.

OBJECTIVES To investigate corneal biomechanical properties and intraocular pressure (IOP) in patients with high myopic anisometropia. METHODS Patients with high myopic anisometropia (n = 23) and emmetropic subjects (n = 55) were enrolled. Corneal hysteresis (CH), Goldmann-correlated intraocular pressure (IOPg), corneal resistance factor, and corneal-compensated IOP (IOPcc) were measured with Ocular Response Analyzer. Central corneal thickness was measured by optical coherence tomography. Zeiss IOL-Master determined the values of corneal refractive power and ocular axial length. RESULTS Significant differences were presented in CH, IOPg, and IOPcc among the high myopic, contralateral, and normal eyes (analysis of variance, P

To determine upper and lower tear menisci using optical coherence tomography (OCT) in volunteers after laser in situ keratomileusis (LASIK) for myopia.Thirty-five eyes of 35 nonsurgical volunteers were evaluated. Twenty-eight eyes of 28 volunteers who underwent LASIK served as the study group. The height, area, and volume of the upper and lower tear menisci were obtained in the study group, using OCT before surgery, 1 week, 1 month, and 20 months after surgery. At each visit, Schirmer test (type I, without anesthesia), tear break-up time, and corneal fluorescein staining score were evaluated. OCT imaging was conducted in the nonsurgical group with the same settings.The lower tear meniscus volume at baseline were significantly smaller in the study group compared with the nonsurgical group (t test, P0.01). The upper tear meniscus volume decreased from 0.44 +/- 0.11 microL to 0.37 +/- 0.08 microL at 1 month after surgery (P0.05). The lower tear meniscus volume (0.54 +/- 0.15 microL) reduced to 0.44 +/- 0.10 microL at 1 month after surgery (posthoc, P0.05). For the subgroup analysis, tear menisci, Schirmer test, and tear break-up time after LASIK decreased during the first 1 month (P0.05) and recovered by 20 months after surgery (t test, P0.05).The upper and lower tear menisci decreased up to 1 month after LASIK and recovered by 20 months. OCT is a useful tool for evaluating the tear system in a noninvasive manner.

Contemporary and classic theories for the accommodative mechanism are based on the concept that the contraction of the ciliary muscle is the initial event that leads to the reshaping of the crystalline lens, an idea initially developed by von Helmholtz.1 The key elements of accommodation, such as the elasticity of the crystalline lens and the activity of the ciliary muscle, decline with age, which degenerates the capacity of accommodation.2–7 Restoring the accommodative ability has been a substantial challenge. The implantation of accommodating intraocular lenses (AIOL) has been shown to restore less than 2 diopters (D) of objective accommodation,8,9 partly due to the difficulty in predicting the dynamic response of the accommodative apparatus during accommodation. The dynamic relationship between ciliary muscle contraction and its ability to reshape the crystalline lens during the real-time processes of the human eye has not been fully studied in vivo, which may further limit the improvements in the restoration of accommodation. Hess10 and Gullstrand11 developed a lenticular theory, which stated that presbyopia was caused by a decrease in the lens reshaping capacity. The ciliary muscle normally contracts in the region where the lens still is capable of a response, but it cannot produce an accommodative response above this level due to the lens hardness, even though muscle still is capable of contracting. In contrast, the extralenticular theory of Duane12,13 showed that a slight weakening of the ciliary muscle decreased the accommodative amplitude. Fincham14,15 proposed a reconciliation of these two extremes, suggesting that the lens is responsible primarily for the loss of accommodation and that the contraction of the ciliary muscle required for lens reshaping increases with age. Although these early theories all predict the age-related changes in muscle-lens relationship, none of them is fully supported. The in vivo assessment of the dynamic response of the crystalline lens to ciliary muscle contraction is critical to understand the mechanism of accommodation and the age-related decline of accommodation. The difficulty in simultaneously imaging the entire anterior segment, including the crystalline lens and ciliary muscle, has limited in vivo studies of accommodation. In nonhuman primate models with iridectomies, the movement of ciliary processes and the lens equator during accommodation has been visualized using goniovideography under the stimulation of the Edinger-Westphal nucleus.16,17 This method may not be applicable to human subjects. Others have used magnetic resonance imaging (MRI), which allows the entire eye (including the ciliary muscle and entire lens) to be imaged, to visualize accommodation.18,19 The low scanning speed limits the application of dynamic measurements in accommodation research. To date, to our knowledge no study has simultaneously assessed the biometric changes in the ciliary muscle and crystalline lens as the function of age in real time in a cohort of human subjects. Optical coherence tomography (OCT) allows the noninvasive and rapid imaging of the ocular anterior segment in the static and dynamic states.20–28 Previously, we developed a system that combined two spectral-domain OCT (SD-OCT) devices.27 One has extended the scan depth to approximately 12 mm in air for the imaging of the entire anterior segment through the pupil, while the other was equipped with a light source that was centered at a wavelength of 1310 nm to image the ciliary muscle in real time. The objective of this study was to investigate the age-related changes in the dynamic responses of human accommodative elements, and the relationship between lens reshaping and muscle contraction during accommodation using the synchronized SD-OCT system.

PURPOSE: Thickness changes of corneal sub-layers after phacoemulsification were investigated by spectral domain ultra-high resolution optical coherence tomography (UHR-OCT). METHODS: The corneas (n = 26) of 26 age-related cataract surgery patients were studied. UHR-OCT was used to evaluate the thickness of Descemet's Endothelium Complex (DEC), stroma, Bowman's layer, epithelium, and full cornea at the center (CCT) before, one day after, and one week after surgery. Non-contact specular microscopy measured CCT, endothelial cell density, and morphology. RESULTS: The DEC, stroma, Bowman's layer, and epithelium were visualized by UHR-OCT. Before surgery, the DEC in all cases appeared as a translucent space between two smooth opaque lines. One day after surgery, the posterior corneal surfaces in half of the eyes were wavy and irregular. Compared to the baseline, one day after surgery the thickness increases of the DEC, stroma, and CCT were 4.3 ± 2.6 µm, 25.5 ± 24.9 µm, and 32.1 ± 26.6 µm, respectively (P < 0.001). The morphology of the DEC and the CCT recovered to baseline one week after surgery (P > 0.05), but endothelial cell density was 8.7% less than at baseline. There were no significant changes in Bowman's layer and epithelium after the operation. The pre-operative DEC thickness was positively correlated with the decreased endothelial cell density at 1 day after surgery (r = 0.55, P = 0.003). CONCLUSIONS: The DEC showed edematous thickening and different degrees of morphological changes after phacoemulsification. The DEC deformation and corneal edema recovered by one week after surgery, which indicated recovery of endothelial function. UHR-OCT is a useful tool to evaluate function of the DEC after phacoemulsification. Pre-operative DEC thickness may indicate the integrity of the endothelium and could be used for predicting endothelial cell loss after phacoemulsification.

To investigate changes of whole eye axial biometry during accommodation using ultra-long scan depth optical coherence tomography (UL-OCT).Prospective, observational case series.Twenty-one adult subjects were enrolled. Using UL-OCT, the left eye of each subject was imaged with relaxed diopters (0 D) and accommodative stimuli (+6 D). Full eye biometry included central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness, vitreous length, and axial length (AL).During accommodation (+6 D), the axial biometry of the whole eye changed significantly. Compared to the rest state, ACD at the accommodative state decreased significantly from 3.128 ± 0.305 mm to 2.961 ± 0.298 mm (paired t test, P.001). The lens thickness increased significantly from 3.723 ± 0.237 mm to 3.963 ± 0.234 mm (P.001). The vitreous length decreased significantly from 17.129 ± 0.864 mm to 17.057 ± 0.848 mm (P.001). AL was 24.519 ± 0.917 mm at the rest state and increased to 24.545 ± 0.915 mm with +6 D accommodation stimulus. The elongated AL of 26.1 ± 13.4 μm between the rest and accommodative states was significant (P.001).During accommodation, whole eye axial biometry changed, including a decrease in ACD and vitreous length and an increase in lens thickness and AL. UL-OCT provides an alternative method that is suitable for full eye biometry during accommodation.

To assess the repeatability of axial biometry of the entire eye using ultra-long scan depth optical coherence tomography (OCT) and to investigate the agreement with IOLMaster measurements (Carl Zeiss Meditec).Prospective, observational case series.There were 37 adult subjects enrolled in group 1 and 12 adult subjects enrolled in group 2. Using ultra-long scan depth OCT, the left eyes of these groups were measured in 2 separate sessions. The images were processed by a manual method and custom-developed automatic software. A model eye was imaged for verification. The subjects in group 2 were imaged using ultra-long scan depth OCT and using the IOLMaster for axial length measurement comparison.All measured parameters of the model eye matched the geometric parameters. In group 1, there were no significant differences in all measured parameters using automatic and manual segmentation methods (P.05, paired t test). The percentage of coefficient of repeatability of segments ranged from 0.3% to 3.9%. The corresponding interclass correlation coefficients ranged from 0.946 to 0.999. The correlation between the results using automatic and manual segmentation methods appeared to be strong (R(2) = 0.999; P.05). In group 2, the axial length of the eye measured by the IOLMaster matched the results obtained by ultra-long scan depth OCT with the automatic method (R1(2) = 0.987; P.05) and the manual method (R2(2) = 0.988; P.05).Automatic axial biometry using ultra-long scan depth OCT successfully measured each segment of the entire eye with good repeatability. With further development of automatic segmentation, ultra-long scan depth OCT seems to be a promising tool in the axial biometry of the entire eye.

We investigated the relationships between the ocular anterior segment biometry and the ocular high-order aberrations (HOAs) during accommodation by combined ultralong scan depth optical coherence tomography (UL-OCT) and wavefront sensor.We enrolled 35 right eyes of young healthy subjects (21 women and 14 men; age, 25.6 ± 3.1 years; spherical equivalent refractive error, -0.41 ± 0.59 diopters [D]). A custom-built UL-OCT and a wavefront sensor were combined. They were able to image the ocular anterior segment and to measure the HOAs during accommodation. The differences in the biometric dimensions and in the HOAs between the nonaccommodative and accommodative states were compared, and the relationships between them were investigated.Compared to the nonaccommodative condition, anterior chamber depth, pupil diameter, and radii of the crystalline lens surface curvatures decreased significantly, while the lens thickness and root-mean-square of high-order aberration (HORMS) of fixed 3-mm pupil size increased under the accommodative stimulus (P0.01). A negative correlation was found between the change in the radius of the lens anterior surface curvature and the change in HORMS (r = -0.370, P = 0.014). For nonaccommodative and accommodative conditions, HORMS for a fixed pupil size was correlated negatively with pupil diameter (r = -0.532 and -0.801, respectively, P0.01).The anterior segment biometry and the HOAs changed significantly during accommodation. The increase in HOAs mainly was due to the increased convexity of the anterior surface of the lens during accommodation. Contraction of the pupil may help to decrease HOAs.

PURPOSE We quantitatively characterized the space between the IOL and the posterior capsule (IOL-PC space) during the early postphacoemulsification period, using high resolution optical coherence tomography (OCT). METHODS We recruited 30 eyes of 30 patients who underwent phacoemulsification and randomly divided them into two groups. Acrysof Natural IQ IOLs were implanted in one group (n = 15), and Adapt-AO IOLs were implanted into the other (n = 15). A custom-built OCT instrument was used to image the IOL-PC space at 1 day, 1 week, and 1 month after surgery. Slit-lamp examination and auto refraction were performed at each visit. RESULTS The IOL-PC spaces in the IQ group were 0.72 ± 0.35, 0.40 ± 0.24, and 0.23 ± 0.16 mm(2) at 1 day, 1 week, and 1 month after surgery, respectively. At each of these times, the values for the AO group were significantly smaller (P < 0.001). Compared to 1 day after surgery, significant changes in the ACDs and refractive errors occurred up to 1 month postoperatively in the IQ group; however, changes in the ACD and refractive error were significant only at 1 week in the AO group. CONCLUSIONS The decreases in IOL-PC space and in ACD during the early postoperative period were associated with a myopic shift. It appeared that the different IOL designs had a role in closure of the IOL-PC space. High resolution OCT was suitable for quantitative analysis of IOL-PC space. (ClinicalTrials.gov number, NCT01605812.).

Aizhu Tao,1,3 Kristen A Peterson,2 Hong Jiang,1 Yilei Shao,1,3 Jianguang Zhong,1,4 Frank C Carey,2 Elias P Rosen,2 Jianhua Wang11Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA; 2Southwest Sciences, Inc, Santa Fe, NM, USA; 3School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China; 4Department of Ophthalmology, Hangzhou First People's Hospital, Hangzhou, People's Republic of ChinaAbstract: We used a unique combination of four state-of-the-art technologies to achieve a high performance spectral domain optical coherence tomography system suitable for imaging the entire ocular surface. An ultra-high resolution, extended depth range, full-phase interferometry, and high-speed complementary metal-oxide semiconductor transistor camera detection provided unprecedented performance for the precise quantification of a wide range of the ocular surface. We demonstrated the feasibility of this approach by obtaining high-speed and high-resolution images of a model eye beyond the corneal–scleral junction. Surfaces determined from the images with a segmentation algorithm demonstrated excellent accuracy and precision.Keywords: ocular surface, complex, full range, optical coherence tomography

This study is designed to test the repeatability of the quantitative analysis of intraretinal layer thickness and cup-disc ratio of the optic nerve head using ultra-high resolution optical coherence tomography (UHR-OCT). Group A, containing 23 eyes of 12 healthy subjects, was imaged twice and group B, containing eight eyes of four subjects, was imaged three times. Intraretinal layers were segmented manually and the cup-to-disc ratio of the optic nerve head was analyzed. Custom-built automatic segmentation software was also used to segment a set of images for comparison. A total of nine intraretinal layers were visualized and extracted manually. With group A, the central foveal thickness was 186.4 ± 15.9 μm (mean ± SD). The average retinal thickness was 296.4 ± 21.3 μm. The best repeatability, obtained when two repeated scans were taken, was obtained for the outer nuclear layer followed by the ganglion cell layer, the inner nuclear layer, the retinal nerve fiber layer and the worst was obtained for the outer segment. The intraclass correlation ranged from 0.824 to 0.997. The coefficients of repeatability ranged from 3.24 to 18.3 μm, corresponding to 1.47% to 26.20%. With group B, high interclass correlations were found and the automatic segmentation results were compatible with the manual results. Our results indicated that more retinal features might be imageable using UHR-OCT.

To investigate by ultrahigh resolution optical coherence tomography the effect of punctal occlusion on tear menisci in symptomatic and asymptomatic contact lens wearers.Symptomatic subjects with self-reported dry eyes (n = 20) and asymptomatic subjects (n = 20) were recruited. For each subject, 1 eye was randomly chosen for both upper and lower punctal occlusion with collagen plugs. Ultrahigh resolution optical coherence tomography imaged both upper and lower tear menisci before punctal occlusion, and 1, 4, 7, and 10 days afterward. Comfort scoring, noninvasive tear break-up time, tear break-up time, and Schirmer test with anesthesia were also performed.Tear meniscus variables in the symptomatic group were lower than those in the asymptomatic group (P0.05) at all time points except for day 4. In the symptomatic group, the tear menisci were increased up to day 4 after punctal occlusion (P0.05). The increase was present only on day 1 in the asymptomatic group. Improvement of comfort scores and noninvasive tear break-up time occurred in both groups after occlusion (P0.05). The comfort scores were linearly correlated with the tear volumes after punctal occlusion, with higher correlation coefficients in the symptomatic group.Punctal occlusion transiently increased tear menisci in symptomatic and asymptomatic lens wearers, with a longer duration in the symptomatic group. For both symptomatic and asymptomatic lens wearers, the increased meniscus volume was associated with improved ocular comfort.

Purpose To determine the relationships among tear menisci variables and clinical tests used in the diagnosis of dry eye patients. Methods Dry eye patients (n=50; age, 35.2 years) and healthy subjects (n=48; age, 33.3 years) were recruited. Upper and lower tear menisci were imaged noninvasively by optical coherence tomography (OCT) immediately after normal and delayed blinking in both eyes. Tear meniscus heights, areas, and radius of curvatures were obtained by custom software. Tear film break-up time was measured by fluorescein (fluorescein film tear break-up time, FTBUT) and tearscope (noninvasive tear film break-up time), ocular surface vital staining was evaluated with fluorescein (FS), and secretion was measured by Schirmer I test without and with anesthesia. Results In dry eye patients, all lower tear meniscus variables during normal blinking were correlated with all clinical tests except Schirmer I test without anesthesia. Upper tear meniscus variables were correlated with FTBUT and Schirmer I test with anesthesia. During delayed blinking, upper and lower tear menisci variables were correlated with Schirmer I test without anesthesia and FS; however, there were no correlations between menisci variables and FTBUT or Schirmer I test with anesthesia. In healthy subjects, only lower meniscus variables were correlated with Schirmer I test with anesthesia during normal blinking. During delayed blinking, the lower meniscus variables were correlated with only the Schirmer I test without anesthesia. Conclusions Lower tear menisci were correlated more strongly with the clinical tests than were upper menisci. The tear menisci were associated with the basic tear secretion during normal blinking. Delayed blinking may affect reflex tearing levels.

Bowman's layer and the basal lamina are important in the maintenance and support of the ocular surface.1 For instance, the integrity of Bowman's layer and the basal lamina prevent the eyes from developing persistent epithelial defects after transplantation.2 Additionally, a cellular proliferative response initiated by disruption of the Bowman's layer and the basal lamina occurs in advanced bullous keratopathy.1 Recently, characteristics of the central and peripheral Bowman's layer, close to the limbus, have drawn increased clinical attention, especially for designing refractive surgery and detecting corneal disease. A variety of techniques have been used to assess Bowman's layer in both healthy and diseased human corneas.3–5 However, each of these methods has some limitations. Confocal microscopy is an invasive technique with the potential of causing corneal lesions or transmitting infections, and it is impossible to measure exactly the same locations within the cornea in serial examinations. Electron microscopy allows only histopathologic findings. Thus, there are only a few published characterizations of Bowman's layer at the periphery, close to the limbus. Recent advances in optical coherence tomography (OCT) have enabled exact and rapid cross-sectional imaging of the cornea without direct contact between the eye and the instrument. OCT has excellent repeatability and accuracy.6–8 Spectral domain OCT (SD-OCT) is an advanced technique that has enhanced resolution compared with conventional time domain OCT. The high-speed imaging modality enables analysis of the topographic thickness of the epithelium, Bowman's layer, stroma, and the total cornea. The purpose of this study was to evaluate by ultra-high resolution SD-OCT the epithelial and Bowman's layer profile along the horizontal meridian in healthy human eyes.

Purpose. To determine the dynamic pre- and postlens tear film (PLTF and PoLTF) thicknesses by using optical coherence tomography (OCT). Methods. Ultrahigh-resolution OCT was used to image the tear film of 22 subjects before and after contact lens wear. A soft lens with 1 drop of artificial tears on its concave surface was inserted onto one randomly selected eye. OCT images were taken before insertion, immediately afterward, and every 2 minutes for 10 minutes. For the contralateral eye, the lens inserted was not prewetted on the concave surface. OCT images were taken before insertion, immediately afterward, and at 3 minutes. Then another drop was instilled, and images were taken immediately afterward and every 2 minutes for 10 minutes. Images were processed by custom software to yield tear film thickness. Results. The thickness of precorneal tear film (PCTF) was 1.9 +/- 0.9 mum. The PoLTF was visualized clearly in all cases immediately after lens insertion, with 1 drop on the lens concave surface. Through the first 6 minutes after insertion, the PoLTF was greater than the PCTF. The PLTF (n = 12) and PoLTF (n = 9) were visualized immediately after lens insertion. After 3 minutes, the PLTF in most subjects and PoLTF in all subjects were invisible. The thickness of the PLTF increased after the instillation of artificial tears, whereas the PoLTF did not at any checkpoint for 10 minutes. Conclusions. Ultrahigh-resolution OCT is a promising tool for measuring the tear film. The PoLTF did not increase after instillation of artificial tears.

Purpose To measure the tear meniscus dynamics in aqueous tear deficiency dry eye patients using optical coherence tomography. Design Clinical research study of a laboratory technique. Methods Twenty-five aqueous tear deficiency dry eye patients and 30 healthy subjects were recruited. Upper and lower tear menisci of 1 randomly selected eye of each participant were imaged during normal and delayed blinking using optical coherence tomography. Measured parameters included upper tear meniscus height and volume, lower tear meniscus height and volume, the blink outcome defined as the meniscus volume change during blink action, and open eye outcome defined as the meniscus volume change during the open eye period. Results During normal blinking, both tear meniscus height and volume before blink in dry eye patients were significantly smaller than those in healthy subjects, except for the upper tear meniscus volume. During normal blinking, the blink outcome and open eye outcome of lower tear meniscus were significantly smaller in dry eye patients compared with healthy subjects. During delayed blinking, the upper and lower tear menisci heights and volumes significantly increased in both groups. However, dry eye patients had smaller increases than healthy subjects. During delayed blinking, the open eye outcomes of upper and lower tear menisci were smaller in dry eye patients than healthy subjects. Conclusions Dry eye patients seem to have reduced tear meniscus dynamics during normal blinking and smaller increases of meniscus volume during delayed blinking. Analysis of tear meniscus dynamics may provide more insight in the altered tear system in dry eye patients.

BACKGROUND AND OBJECTIVE: To develop a prototype three-dimensional anterior segment spectral-domain optical coherence tomography (SD-OCT) device and demonstrate the feasibility of its use in the operating room. PATIENTS AND METHODS: Single-institution interventional case series including six consecutive patients undergoing Descemet's stripping automated endothelial keratoplasty (DSAEK). The prototype anterior segment SD-OCT was used intraoperatively to search for the presence of interface fluid between the host cornea and the DSAEK graft. RESULTS: Anterior segment SD-OCT was successfully used intraoperatively during DSAEK. After the initial placement of the graft, no fluid was clinically apparent; however, interface fluid was identified by anterior segment SD-OCT in two of the six cases. After additional aspiration, all patients were fluid-free on follow-up anterior segment SD-OCT scanning. CONCLUSION: Intraoperative anterior segment SD-OCT was used successfully to find interface fluid that was clinically undetectable under the microscope. As such, all patients were able to leave the operating room with a fully attached graft. [Ophthalmic Surg Lasers Imaging 2010;41:250–254.]

PURPOSE To investigate the fluctuations of directly measured intraocular pressure (IOP) and induced diastolic ocular perfusion pressure (DOPP) during three simulated steps of phacoemulsification in vivo. METHODS Twenty-five eyes of 25 patients who underwent phacoemulsification were evaluated. A pressure transducer was inserted into the anterior chamber to measure IOP directly. The cortical cleanup and viscoelastic removal, nuclear disassembly, and anterior capsular polishing stages of phacoemulsification were simulated. Baseline, static, and dynamic IOP measurements at each stage were conducted before a routine phacoemulsification procedure was performed. DOPP was determined as the difference between diastolic blood pressure and IOP. RESULTS The directly measured IOP fluctuated from 13 +/- 4.7 to 96 +/- 6.2 mm Hg during the simulated steps of phacoemulsification (repeated-measurement ANOVA, P < 0.001). It was elevated more than 39 mm Hg compared with the baseline in static and dynamic measurements (post hoc, P < 0.001). Static DOPPs were lower than 0 mm Hg in all cases during simulated cortical cleanup and viscoelastic removal and in 19 cases during simulated nuclear disassembly. Dynamic DOPPs were lower than 0 mm Hg in 14 cases during simulated cortical cleanup and viscoelastic removal. CONCLUSIONS IOP and DOPP fluctuate widely during simulated steps of phacoemulsification. Further studies may be needed to establish the effect of the transient fluctuations in DOPP on visual function.

PURPOSE To determine the vertical and horizontal thickness profiles of the corneal epithelium in vivo using ultra-long scan depth and ultra-high resolution spectral domain optical coherence tomography (SD-OCT). METHODS A SD-OCT was developed with an axial resolution of ∼ 3.3 µm in tissue and an extended scan depth. Forty-two eyes of 21 subjects were imaged twice. The entire horizontal and vertical corneal epithelial thickness profiles were evaluated. The coefficient of repeatability (CoR) and intraclass correlation (ICC) of the tests and interobserver variability were analyzed. RESULTS The full width of the horizontal epithelium was detected, whereas part of the superior epithelium was not shown for the covered super eyelid. The mean central epithelial corneal thickness was 52.0 ± 3.2 µm for the first measurement and 52.3 ± 3.4 µm for the second measurement (P>.05). In the central zone (0-3.0 mm), the paracentral zones (3.0-6.0 mm) and the peripheral zones (6.0-10.0 mm), the mean epithelial thickness ranged from 51 to 53 µm, 52 to 57 µm, and 58 to 72 µm, respectively. There was no difference between the two tests at both meridians and in the right and left eyes (P>.05). The ICCs of the two tests ranged from 0.70 to 0.97 and the CoRs ranged from 2.5 µm to 7.8 µm from the center to the periphery, corresponding to 5.6% to 10.6% (CoR%). The ICCs of the two observers ranged from 0.72 to 0.93 and the CoRs ranged from 4.5 µm to 10.4 µm from the center to the periphery, corresponding to 8.7% to 15.2% (CoR%). CONCLUSIONS This study demonstrated good repeatability of ultra-high resolution and long scan depth SD-OCT to evaluate the entire thickness profiles of the corneal epithelium. The epithelial thickness increases from the center toward the limbus.

We demonstrated a novel approach of imaging the anterior segment including the ciliary muscle using combined and synchronized two spectral domain optical coherence tomography devices (SD-OCT). In one SD-OCT, a Complementary Metal-Oxide-Semiconductor Transistor (CMOS) camera and an alternating reference arm was used to image the anterior segment from the cornea to the lens. Another SD-OCT for imaging the ciliary muscle was equipped with a light source with a center wavelength of 1,310 nm and a bandwidth of 75 nm. Repeated measurements were performed under relaxed and 4.00 D accommodative stimulus states in six eyes from 6 subjects. We also imaged dynamic changes in the anterior segment in one eye during accommodation. The biometry of the anterior segment and the ciliary muscle was obtained. The combined system appeared to be capable to simultaneously real-time image the biometry of the anterior segment, including the ciliary muscle, in vivo during accommodation.

Purpose Our purpose was to investigate the role of the axial resolution of optical coherence tomography (OCT) on the measurement of corneal and epithelial thickness by evaluating the repeatability and agreement among different OCT devices with different axial resolutions. Methods twenty right eyes of 20 healthy subjects (AGE: 22.3 ± 1.3 years) and 18 eyes of 18 patients (age: 25.7 ± 6.8 years) after laser in situ keratomileusis (LASIK) refractive surgery were tested. Each subject was imaged using four OCT devices: ultra-high resolution OCT (UHR-OCT), ultra-long scan depth OCT (UL-OCT), commercial RTVue, and Visante. The OCT images obtained from UHR-OCT, UL-OCT, and RTVue were processed with a custom automated algorithm for measuring the central corneal thickness (CCT) and central epithelial thickness (ET). CCT measurements from pachymetry maps that were generated by RTVue and Visante were also obtained. Results For both groups, the CCT and ET measured by UHR-OCT and UL-OCT were highly correlated with RTVue when the automated image processing algorithm was used. The CCT measurements from the RTVue and Visante pachymetry were thicker than those measurements obtained from the automatic algorithm. The coefficient of repeatability was less than 4.9 μm in the healthy subjects and 7.9 μm in the LASIK patients, and the associated intraclass correlation coefficient (ICC) was greater than 0.992 in both groups for the CCT measurements. For the ET measurements using UHR-OCT, UL-OCT and RTVue, the coefficient of repeatability was less than 2.2 μm in the healthy subjects and 4.8 μm in the LASIK patients with an ICC that was greater than 0.84. Conclusions The axial resolution of OCT may play a role in determining the precision with which the CCT and the ET can be measured, although it may not affect the measurement of results.

PURPOSE To measure the upper and lower tear menisci in patients with aqueous tear deficiency (ATD) dry eye by real-time optical coherence tomography (OCT) and to determine the most effective meniscus variables for the diagnosis of dry eye. METHODS Eyes of 48 pre-screened ATD patients were compared with those of 47 healthy subjects. Upper and lower tear menisci were imaged simultaneously by real-time OCT immediately after blinking. The height, radius, and cross-sectional area of upper and lower tear menisci were obtained. RESULTS The tear meniscus radius, height, and cross-sectional area were significantly smaller in patients with dry eye than in healthy subjects (P < 0.01). The lower tear meniscus variables were higher than the upper menisci (P < 0.01) in normal subjects; however, no significant differences between menisci were found in ATD patients. In both groups, the upper and lower tear meniscus variables were strongly correlated with each other. Good dry eye diagnostic accuracies were obtained with cutoff values for an abnormal lower tear meniscus radius (LTMR) of 182 microm and a lower tear meniscus height (LTMH) of 164 microm. The LTMR diagnostic sensitivity and specificity were 0.92 and 0.87, respectively. The LTMH diagnostic sensitivity and specificity were 0.92 and 0.90. CONCLUSIONS Upper tear meniscus variables in ATD patients were assessed by real-time OCT. The tear meniscus was smaller in ATD patients than in healthy subjects. LTMR and LTMH may have potential in the diagnosis of ATD.

To determine diurnal variation of tear menisci around upper and lower eyelids in normal subjects.Prospective laboratory investigation.Twenty young healthy Chinese subjects (10 women and 10 men; mean age, 21.3 years; range, 20 to 26 years) with no history of contact lens wear or previously diagnosed dry eye were recruited. A custom-built, real-time anterior segment optical coherence tomography (OCT) instrument was used simultaneously to image the upper and lower tear menisci. Repeated measurements immediately after blinking were conducted on both eyes during a 24-hour period, including immediately before and after sleeping. Dimensional information of the tear menisci were obtained from the OCT images using custom software.There were no significant differences between right and left menisci, nor were there any differences between females and males in the lower tear meniscus (P.05, repeated-measurement analysis of variance [ANOVA]). Although the lower tear meniscus variables were correlated strongly with upper meniscus variables, the lower meniscus was significantly greater than the upper one. Significant diurnal variations (P.05, repeated-measurement ANOVA) of all measured variables were observed during the study period. Tear menisci were significantly increased at eye opening after overnight sleep compared with the baseline before sleep at 10 pm (P.001, post hoc tests). They remained elevated up to 10 minutes after eye opening (P.001, post hoc tests).Real-time OCT can provide useful information regarding the dynamics of the tear system. Diurnal variation of the upper and lower tear menisci occur.