Ocular blood flow in preterm neonates.

Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.

Correlation of Ocular Plane-Wave Doppler With Optical Coherence Tomography Angiography in Preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a severe complication of pregnancy characterized by hypertension, proteinuria and compromised fetal blood supply. The eye, like other end organs, is affected by this systemic condition, but unlike in other organs, ocular media transparency allows high-resolution optical visualization of the vascular structure of the retina. Our aim was to assess how ultrasound-determined ocular blood-flow correlates with vascular structure of the retina and choriocapillaris determined by optical coherence tomography angiography (OCTA). METHODS: Plane-wave ultrasound and OCTA were performed on both eyes of 40 consecutive subjects consisting of normal controls (n = 11), mild PE (n = 5), severe PE (n = 17) and chronic or gestational hypertension (n = 7) within 72 hours following delivery. From ultrasound, we measured pulsatile flow velocity and resistance indices in the central retinal artery (CRA) and vein, the short posterior ciliary arteries (SPCAs) and choroid. From OCTA, we measured vascular density (VD) in the superficial, deep retina and choriocapillaris. We determined differences in Doppler and OCTA parameters among groups and correlations between ultrasound and OCTA. RESULTS: In severe PE, flow resistance was reduced with respect to controls. Flow velocity and resistance in the and SPCA were moderately correlated with VD in the choriocapillaris and peripapillary retina, but VD in PE did not differ significantly from controls. CONCLUSIONS: Although OCTA parameters were moderately correlated with Doppler ultrasound, OCTA did not demonstrate significant differences between PE and controls postpartum.

High-Frequency Ultrasound Activation of Perfluorocarbon Nanodroplets for Treatment of Glaucoma.

Elevated intraocular pressure (IOP) is the most prevalent risk factor for initiation and progression of neurodegeneration in glaucoma. Ocular hypertension results from increased resistance to aqueous fluid outflow caused by reduced porosity and increased stiffness of tissues of the outflow pathway. Acoustic activation and resulting bioeffects of the perfluorocarbon (PFC) nanodroplets (NDs) introduced into the anterior chamber (AC) of the eye could potentially represent a treatment for glaucoma by increasing permeability in the aqueous outflow track. To evaluate the potential of NDs to enter the outflow track, 100-nm diameter perfluoropentane (PFP) NDs with a lipid shell were injected into the AC of ex vivo pig eyes and in vivo rat eyes. The NDs were activated and imaged with 18- and 28-MHz linear arrays to assess their location and diffusion. NDs in the AC could also be visualized using optical coherence tomography (OCT). Because of their higher density with respect to aqueous humor, some NDs settled into the iridocorneal angle where they entered the outflow pathway. After acoustic activation of the NDs at the highest acoustic pressure, small gas bubbles were observed in the AC. After two days, no acoustic activation events were visible in the AC of the rats and their eyes showed no evidence of inflammation.

Ocular Blood Flow in Preterm Neonates: A Preliminary Report.

Purpose: Retinopathy of prematurity (ROP) is a vision-threatening complication occurring in pre-term neonates. The standard of care entails regular monitoring by dilated ophthalmoscopy examinations, which entail stress and potential morbidity. In this pilot study, we used plane-wave ultrasound (PWUS) to image, measure, and assess the association of blood-flow velocities in the retrobulbar vessels with ROP stages ranging from stage 0 (immature vessels without ROP) to stage 3. Methods: Both eyes of 14 preterm neonates at risk for ROP were examined by 18 MHz PWUS. All but two subjects had a follow-up examination. PWUS was acquired for 1.5 seconds at 3000 compound B-scans/sec. Data were postprocessed to form color-flow images and spectrograms depicting flow velocity in the central retinal artery (CRA), central retinal vein (CRV), and the short posterior ciliary arteries (SPCA). Flow parameters derived from spectrograms were compared by ROP stage. Results: ROP stage was found to correlate with flow velocities. Velocities were significantly elevated with respect to non-ROP eyes in all vessels at stage 3 and in the SPCAs at stage 2. Conclusions: PWUS measurement of blood flow may provide a quantitative, clinically important, and easily tolerated means for detecting and assessing the risk of ROP in preterm neonates. We speculate that the observed increase in flow velocity results from elevated vascular endothelial growth factor (VEGF) in ROP eyes. Translational Relevance: PWUS offers a gentle, nonmydriatic method for monitoring neonates at risk for ROP that would complement ophthalmoscopy.

Retrobulbar blood flow in rat eyes during acute elevation of intraocular pressure.

Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in the orbit overall. Systolic, diastolic and mean velocities and resistive and pulsatile indices were determined from arterial spectrograms at each IOP level. Baseline mean arterial and mean venous velocities averaged 30.9 ±â€¯10.8 and 8.5 ±â€¯3.3 mm/s, respectively. Arterial velocity progressively decreased and resistance indices increased at and above an IOP of 30 mmHg. Mean arterial velocity at 60 mmHg dropped by 55% with respect to baseline, while venous velocity decreased by 20%. Arterial and venous velocities and resistance returned to near baseline after IOP was restored to 10 mmHg. Both vascular density and orbital perfusion decreased with IOP, but while perfusion returned to near normal when IOP returned to 10 mmHg, density remained reduced. Our findings are consistent with OCT-based studies showing reduced perfusion of the retina at levels comparable to retrobulbar arterial flow velocity change with increased IOP. The lesser effect on venous flow is possibly attributable to partial collapse of the venous lumen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies.

Compound Coherent Plane-Wave Ultrasound Imaging of Vascular Malformations of the Orbit.

PURPOSE: Prior color-flow Doppler ultrasound studies of the eye have been performed with systems that exceed US Food and Drug Administration permissible ophthalmic ultrasonic energy limits. The authors report a study of orbital vascular malformations using a novel, Food and Drug Administration compliant, ultrafast compound coherent plane-wave ultrasound device to produce power Doppler images. METHODS: Using a Verasonics Vantage 128 ultrasound engine and a user-developed MATLAB program with a 5-MHz linear-array probe, compound coherent plane-wave ultrasound data were collected on patients with orbital vascular malformations. Real-time color-flow Doppler visualized orbital blood flow. Power Doppler images were produced by post-processing compound coherent plane-wave ultrasound data acquired continuously for 2 seconds. RESULTS: Compound coherent plane-wave ultrasound was performed on 3 orbital vascular malformations (1 venolymphatic malformation, 1 infantile hemangioma, and 1 arteriovenous malformation). Compound coherent plane-wave ultrasound produced a high-resolution depiction of orbital blood flow for orbital vascular malformations with high sensitivity to slow flow. CONCLUSIONS: Analysis of blood flow within orbital lesions informs treatment planning. Compound coherent plane-wave ultrasound is an emerging ultrasound modality that falls within the Food and Drug Administration guidelines for use in the orbit and provides information to characterize orbital vascular malformations.

Plane-Wave Ultrasound Doppler of the Eye in Preeclampsia.

Purpose: Pre-eclampsia (PE) is a serious complication of pregnancy characterized by high blood pressure, proteinuria, compromised fetal blood supply, and potential organ damage. The superficial location of the eye makes it an ideal target for characterization hemodynamics. Our aim was to discern the impact of PE on ocular blood flow. Methods: 18 MHz plane-wave ophthalmic ultrasound scanning was performed on subjects with PE (n = 26), chronic or gestational hypertension (n = 8), and normal controls (n = 19) within 72 hours of delivery. Duplicate three-second long scans of the posterior pole including the optic nerve were acquired at 6000 images/sec for evaluation of the central retinal artery and vein and the short posterior ciliary arteries. The choroid was scanned at 1000 images/sec. Doppler analysis provided values of pulsatile flow velocity and resistance indexes. Results: End diastolic velocity was higher, and pulsatility and resistive indexes were significantly lower in the choroid, central retinal artery and short posterior ciliary arteries in PE than in controls. Blood pressure was elevated in PE with respect to controls and was negatively correlated with resistance. Conclusions: Although vasoconstriction is considered characteristic of PE, we found reduced resistance in the orbital vessels and choroidal arterioles, implying vasodilation at this level. Future studies incorporating optical coherence tomography angiography for characterization of the retina and choriocapillaris in conjunction with plane-wave ultrasound scanning, particularly in late pregnancy, might address this conundrum. Translational Relevance: Use of plane-wave ultrasound scanning for evaluation ocular blood flow in women at risk for PE may offer an avenue towards early detection and clinical intervention.

Contrast-enhanced plane-wave ultrasound imaging of the rat eye.

Preclinical imaging, especially of rodent models, plays a major role in experimental ophthalmology. Our aim was to determine if ultrasound can be used to visualize and measure flow dynamics in the retrobulbar vessels supplying and draining the eye and the potential of contrast microbubbles to provide image and measurement enhancement. To accomplish this, we used a 128-element, 18 MHz linear array ultrasound probe and performed plane-wave imaging of the eyes of Sprague Dawley rats. Compound images were acquired by emitting unfocused wavefronts at multiple angles and combining echo data from all angles to form individual B-scans. Multiple imaging sequences were utilized, compounding up to six angles, with imaging rate of up to 3000 compound B-scans per second and sequence durations from 1.5 to 180 s. Data were acquired before and after intravenous introduction of contrast microbubbles. We found the total power of the Doppler signal in the image plane to increase approximately 20 fold after injection of contrast, followed by an exponential decay to baseline in about 90 s, The best-fit time constant of the decay averaged 41 s. While major vessels and the retinal/choroidal complex were evident pre-contrast, they were dramatically enhanced with contrast present, with details such as choroidal arterioles seen only with contrast. Ocular arteriovenous transit time determined from comparative enhancement curves in arteries and veins was approximately 0.2 s. In conclusion, plane wave ultrasound, especially with enhancement by contrast microbubbles, offers a means for the study of ocular hemodynamics using the rat eye as a model.

Ultrasound Imaging and Measurement of Choroidal Blood Flow.

PURPOSE: The choroid is a vascular network providing the bulk of the oxygen and nutrient supply to the retina and may play a pivotal role in retinal disease pathogenesis. While optical coherence tomography angiography provides an en face depiction of the choroidal vasculature, it does not reveal flow dynamics. In this report, we describe the use of plane-wave ultrasound to image and characterize choroidal blood flow. METHODS: We scanned both eyes of 12 healthy subjects in a horizontal plane superior to the optic nerve head using an 18-MHz linear array. Plane-wave data were acquired over 10 transmission angles that were coherently compounded to produce 1000 images/sec for 3 seconds. These data were processed to produce a time series of power Doppler images and spectrograms depicting choroidal flow velocity. Analysis of variance was used to characterize peak systolic, and end diastolic velocities and resistive index, and their variability between scans, eyes, and subjects. RESULTS: Power Doppler images showed distinct arterioles within a more diffuse background. Choroidal flow was moderately pulsatile, with peak systolic velocity averaging approximately 10 mm/sec and resistive index of 0.55. There was no significant difference between left and right eyes, but significant variation among subjects. CONCLUSIONS: Plane-wave ultrasound visualized individual arterioles and allowed measurement of flow over the cardiac cycle. Characterization of choroidal flow dynamics offers a novel means for assessment of the choroid's role in ocular disease. TRANSLATIONAL RELEVANCE: Characterization of choroidal flow dynamics offers a novel means for assessment of the choroid's role in ocular disease.

Improved High-Frequency Ultrasound Corneal Biometric Accuracy by Micrometer-Resolution Acoustic-Property Maps of the Cornea.

PURPOSE: Mapping of epithelial thickness (ET) is useful for detection of keratoconus, a disease characterized by corneal thinning and bulging in which epithelial thinning occurs over the apex. In prior clinical studies, optical coherence tomography (OCT) measurements of ET were systematically thinner than those obtained by 40-MHz high-frequency ultrasound (HFU) where a constant speed of sound (c) of 1636 m/s was used for all corneal layers. The purpose of this work was to study the acoustic properties, that is, c, acoustic impedance (Z), and attenuation (α) of the corneal epithelium and stroma independently using a scanning acoustic microscope (SAM) to investigate the discrepancy between OCT and HFU estimates of ET. METHODS: Twelve unfixed pig corneas were snap-frozen and 6-µm sections were scanned using a custom-built SAM with an F-1.08, 500-MHz transducer and a 264-MHz bandwidth. Two-dimensional maps of c, Z, and α with a spatial resolution of 4 µm were derived. RESULTS: SAM showed that the value of c in the epithelium (i.e., 1548 ± 18 m/s) is substantially lower than the value of c in the stroma (i.e., 1686 ± 33 m/s). CONCLUSION: SAM results demonstrated that the assumption of a constant value of c for all corneal layers is incorrect and explains the prior discrepancy between OCT and HFU ET determinations. TRANSLATIONAL RELEVANCE: The findings of this study have important implications for HFU-based ET measurements and will improve future keratoconus diagnosis by providing more-accurate ET estimates.

Combined tomography and epithelial thickness mapping for diagnosis of keratoconus.

PURPOSE: Scanning Scheimpflug provides information regarding corneal thickness and 2-surface topography while arc-scanned high-frequency ultrasound allows depiction of the epithelial and stromal thickness distributions. Both techniques are useful in detection of keratoconus. Our aim was to develop and test a keratoconus classifier combining information from both methods. METHODS: We scanned 111 normal and 30 clinical keratoconus subjects with Artemis-1 and Pentacam data. After selecting one random eye per subject, we performed stepwise linear discriminant analysis on a dataset combining parameters generated by each method to obtain classification models based on each technique alone and in combination. RESULTS: Discriminant analysis resulted in a 4-variable model (R2 = 0.740) based on Artemis data alone and a 4-variable model (R2 = 0.734) using Pentacam data alone. The combined model (R2 = 0.828) consisted of 3 Artemis- and 4 Pentacam-derived variables. The combined model R value was significantly higher than either model alone (p = 0.031, one-tailed). In cross-validation, Artemis had 100% sensitivity and 99.2% specificity, Pentacam had 97.3% sensitivity and 98.0% specificity, and the combined model had 97.3% sensitivity and 100% specificity. CONCLUSIONS: Pentacam, Artemis, and combined models were all effective in distinguishing normal from clinical keratoconus subjects. From the standpoint of variance explained by the model (R2 values), the combined model was most effective. Application of the model to early and subclinical keratoconus will ultimately be required to assess the effectiveness of the combined approach.

Ultrafast Ultrasound Imaging of Ocular Anatomy and Blood Flow.

PURPOSE: Ophthalmic ultrasound imaging is currently performed with mechanically scanned single-element probes. These probes have limited capabilities overall and lack the ability to image blood flow. Linear-array systems are able to detect blood flow, but these systems exceed ophthalmic acoustic intensity safety guidelines. Our aim was to implement and evaluate a new linear-array-based technology, compound coherent plane-wave ultrasound, which offers ultrafast imaging and depiction of blood flow at safe acoustic intensity levels. METHODS: We compared acoustic intensity generated by a 128-element, 18-MHz linear array operated in conventionally focused and plane-wave modes and characterized signal-to-noise ratio (SNR) and lateral resolution. We developed plane-wave B-mode, real-time color-flow, and high-resolution depiction of slow flow in postprocessed data collected continuously at a rate of 20,000 frames/s. We acquired in vivo images of the posterior pole of the eye by compounding plane-wave images acquired over ±10° and produced images depicting orbital and choroidal blood flow. RESULTS: With the array operated conventionally, Doppler modes exceeded Food and Drug Administration safety guidelines, but plane-wave modalities were well within guidelines. Plane-wave data allowed generation of high-quality compound B-mode images, with SNR increasing with the number of compounded frames. Real-time color-flow Doppler readily visualized orbital blood flow. Postprocessing of continuously acquired data blocks of 1.6-second duration allowed high-resolution depiction of orbital and choroidal flow over the cardiac cycle. CONCLUSIONS: Newly developed high-frequency linear arrays in combination with plane-wave techniques present opportunities for the evaluation of ocular anatomy and blood flow, as well as visualization and analysis of other transient phenomena such as vessel wall motion over the cardiac cycle and saccade-induced vitreous motion.

Comparison of very-high-frequency ultrasound and spectral-domain optical coherence tomography corneal and epithelial thickness maps.

PURPOSE: To compare corneal thickness and epithelial thickness measurements in maps obtained using the RTVue spectral domain optical coherence tomography (SD-OCT) system and the Artemis 2 immersion arc-scanning very-high-frequency ultrasound (VHF-US) system. SETTING: Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA. DESIGN: Comparative study. METHODS: Eyes of normal volunteers were scanned with the SD-OCT system followed by the VHF-US system and then again by the SD-OCT system. On each map, the minimum corneal thickness and mean values of corneal thickness and epithelial thickness in the 3.0 mm radius zone and in 0.5 mm wide concentric annuli of up to a 3.0 mm radius around the corneal vertex were determined. RESULTS: Both eyes of 12 normal volunteers were scanned. The corneal thickness values from both devices were highly correlated (R > 0.96); in the 3.0 mm radius zone, they were not statistically significantly different. There was no statistically significant change in epithelial thickness or corneal thickness in SD-OCT measurements taken before versus after immersion US. Although highly correlated (R > 0.76), the SD-OCT epithelial thickness values were systematically thinner (1.7 ± 2.1 µm) than the VHF-US measurements in the 3.0 mm radius zone (P < .01). CONCLUSIONS: The corneal thickness measurements in the 3.0 mm radius zone in normal eyes were equivalent between the 2 systems. Although correlated, the VHF-US epithelial thickness measurements were systemically thicker than the SD-OCT values. FINANCIAL DISCLOSURES: Drs. Silverman and Reinstein have a commercial interest in Arcscan, Inc. Dr. Reinstein is a consultant to Carl Zeiss Meditec. None of the other authors has a financial or proprietary interest in any material or method presented.

In vivo imaging of ocular blood flow using high-speed ultrasound.

Clinical ophthalmic ultrasound is currently performed with mechanically scanned, single-element probes, but these are unable to provide useful information about blood flow with Doppler techniques. Linear arrays are well-suited for the detection of blood flow, but commercial systems generally exceed FDA ophthalmic safety limits. A high-speed plane-wave ultrasound approach with an 18-MHz linear array was utilized to characterize blood flow in the orbit and choroid. Acoustic intensity was measured and the plane-wave mode was within FDA limits. Data were acquired for up to 2 sec and up to 20,000 frames/s with sets of steered plane-wave transmissions that spanned 2*θ degrees where 0 degrees was normal to the array. Lateral resolution was characterized using compounding from 1 to 50 transmissions and -6-dB lateral beamwidths ranged from 320 to 180 µm, respectively. Compounded high-frame-rate data were post-processed using a singular value decomposition spatiotemporal filter and then flow was estimated at each pixel using standard Doppler processing methods. A 1-cm diameter rotating scattering phantom and a 2-mm diameter tube with a flow of blood-mimicking fluid were utilized to validate the flow-estimation algorithms. In vivo data were obtained from the posterior pole of the human eye which revealed regions of flow in the choroid and major orbital vessels supplying the eye.

Detection of Keratoconus in Clinically and Algorithmically Topographically Normal Fellow Eyes Using Epithelial Thickness Analysis.

PURPOSE: To assess the effectiveness of a keratoconus-detection algorithm derived from Artemis very high-frequency (VHF) digital ultrasound (ArcScan Inc., Morrison, CO) epithelial thickness maps in the fellow eye from a series of patients with unilateral keratoconus. METHODS: The study included 10 patients with moderate to advanced keratoconus in one eye but a clinically and algorithmically topographically normal fellow eye. VHF digital ultrasound epithelial thickness data were acquired and a previously developed classification model was applied for identification of keratoconus to the clinically normal fellow eyes. Pentacam (Oculus Optikgeräte, Wetzlar, Germany) Belin-Ambrósio Enhanced Ectasia Display "D" score (BAD-D) data (5 of 10 eyes), and Orbscan (Bausch & Lomb, Rochester, NY) SCORE data (9 of 10 eyes) were also evaluated. RESULTS: Five of the 10 fellow eyes were classified as keratoconic by the VHF digital ultrasound epithelium model. Five of 9 fellow eyes were classified as keratoconic by the SCORE model. For the 5 fellow eyes with Pentacam and VHF digital ultrasound data, one was classified as keratoconic by the VHF digital ultrasound model, one (different) eye by a combined VHF digital ultrasound and Pentacam model, and none by BAD-D alone. CONCLUSIONS: Under the assumption that keratoconus is a bilateral but asymmetric disease, half of the 'normal' fellow eyes could be found to have keratoconus using epithelial thickness maps. The Orbscan SCORE or the combination of topographic BAD-D criteria with epithelial maps did not perform better.

Acoustic radiation force for noninvasive evaluation of corneal biomechanical changes induced by cross-linking therapy.

OBJECTIVES: To noninvasively measure changes in corneal biomechanical properties induced by ultraviolet-activated riboflavin cross-linking therapy using acoustic radiation force (ARF). METHODS: Cross-linking was performed on the right eyes of 6 rabbits, with the left eyes serving as controls. Acoustic radiation force was used to assess corneal stiffness before treatment and weekly for 4 weeks after treatment. Acoustic power levels were within US Food and Drug Administration guidelines for ophthalmic safety. Strain, determined from ARF-induced displacement of the front and back surfaces of the cornea, was fit to the Kelvin-Voigt model to determine the elastic modulus (E) and coefficient of viscosity (η). The stiffness factor, the ratio of E after treatment to E before treatment, was calculated for treated and control eyes. At the end of 4 weeks, ex vivo thermal shrinkage temperature analysis was performed for comparison with in vivo stiffness measurements. One-way analysis of variance and Student t tests were performed to test for differences in E, η, the stiffness factor, and corneal thickness. RESULTS: Biomechanical stiffening was immediately evident in cross-linking-treated corneas. At 4 weeks after treatment, treated corneas were 1.3 times stiffer and showed significant changes in E (P= .006) and η (P= .007), with no significant effect in controls. Corneal thickness increased immediately after treatment but did not differ significantly from the pretreatment value at 4 weeks. CONCLUSIONS: Our findings demonstrate a statistically significant increase in stiffness in cross-linking-treated rabbit corneas based on in vivo axial stress/strain measurements obtained using ARF. The capacity to noninvasively monitor corneal stiffness offers the potential for clinical monitoring of cross-linking therapy.

Epithelial remodeling as basis for machine-based identification of keratoconus.

PURPOSE: To develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data. METHODS: Maps of the corneal epithelial and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier. RESULTS: Stepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade. CONCLUSIONS: The results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas.

Comparison of artemis 2 ultrasound and Visante optical coherence tomography corneal thickness profiles.

PURPOSE: To compare corneal thickness profiles of cross-sections of cornea determined by arc-scanned immersion ultrasound and optical coherence tomography (OCT). METHODS: Corneas of 28 eyes from 14 participants were scanned in triplicate using the Artemis 2 high-frequency arc-scanned ultrasound system (ArcScan Inc) and the Visante OCT system (Carl Zeiss Meditec). Corneal thickness and reproducibility were compared within 3.5 mm of central cornea in the horizontal plane. RESULTS: Although highly correlated, Visante central and peripheral corneal thickness values were systematically thinner than Artemis 2 values. Within the central 0.5 mm, the difference was approximately 8 µm, but the difference increased with distance from the center. Reproducibility for each instrument was comparable, measuring <4 µm centrally and increasing peripherally. CONCLUSIONS: Visante OCT measurements of corneal thickness are thinner than Artemis 2 ultrasound values centrally with an increasing difference with peripheral position. Measurement reproducibility was comparable for the two techniques.

Effect of ultrasound radiation force on the choroid.

PURPOSE: While visualization of the retina and choroid has made great progress, functional imaging techniques have been lacking. Our aim was to utilize acoustic radiation force impulse (ARFI) response to probe functional properties of these tissues. METHODS: A single element 18-MHz ultrasound transducer was focused upon the retina of the rabbit eye. The procedure was performed with the eye proptosed and with the eye seated normally in the orbit. The transducer was excited to emit ARFI over a 10-ms period with a 25% duty cycle. Phase resolved pulse/echo data were acquired before, during, and following ARFI. RESULTS: In the proptosed eye, ARFI exposure produced tissue displacements ranging from 0 to 10 µm, and an immediate increase in choroidal echo amplitude to over 6 dB, decaying to baseline after about 1 second. In the normally seated eye, ultrasound phase shifts consistent with flow were observed in the choroid, but enhanced backscatter following ARFI rarely occurred. ARFI-induced displacements of about 10 µm were observed at the choroidal margins. Larger displacements occurred within the choroid and in orbital tissues. CONCLUSIONS: We hypothesize that elevated intraocular pressure occurring during proptosis induced choroidal ischemia and that acoustic radiation force produced a transient local decompression and reperfusion. With the eye normally seated, choroidal flow was observed and little alteration in backscatter resulted from exposure. Clinical application of this technique may provide new insights into diseases characterized by altered choroidal hemodynamics, including maculopathies, diabetic retinopathy, and glaucoma.

Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens.

PURPOSE: To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. METHODS: Profiles of whole isolated human lenses (n=30) aged 20-69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-co-ordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. RESULTS: Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 microm. The age-dependent equations provide a reliable lens model for ages 20-60 years. CONCLUSION: The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens.