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.

Ultrasound Assessment of Gaze-induced Posterior Eyewall Deformation in Highly Myopic Eyes.

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma. Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed. Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (ß = 0.050, P < 0.001) and absolute value of KMax (ß = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The ß coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L. Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

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.

Pulsatility and flow patterns across macro- and microcirculatory arteries of continuous-flow left ventricular assist device patients.

BACKGROUND: Reduced arterial pulsatility in continuous-flow left ventricular assist devices (CF-LVAD) patients has been implicated in clinical complications. Consequently, recent improvements in clinical outcomes have been attributed to the "artificial pulse" technology inherent to the HeartMate3 (HM3) LVAD. However, the effect of the "artificial pulse" on arterial flow, transmission of pulsatility into the microcirculation and its association with LVAD pump parameters is not known. METHODS: The local flow oscillation (pulsatility index, PI) of common carotid arteries (CCAs), middle cerebral arteries (MCAs) and central retinal arteries (CRAs-representing the microcirculation) were quantified by 2D-aligned, angle-corrected Doppler ultrasound in 148 participants: healthy controls, n = 32; heart failure (HF), n = 43; HeartMate II (HMII), n = 32; HM3, n = 41. RESULTS: In HM3 patients, 2D-Doppler PI in beats with "artificial pulse" and beats with "continuous-flow" was similar to that of HMII patients across the macro- and microcirculation. Additionally, peak systolic velocity did not differ between HM3 and HMII patients. Transmission of PI into the microcirculation was higher in both HM3 (during the beats with "artificial pulse") and in HMII patients compared with HF patients. LVAD pump speed was inversely associated with microvascular PI in HMII and HM3 (HMII, r2 = 0.51, p < 0.0001; HM3 "continuous-flow," r2 = 0.32, p = 0.0009; HM3 "artificial pulse," r2 = 0.23, p = 0.007), while LVAD pump PI was only associated with microcirculatory PI in HMII patients. CONCLUSIONS: The "artificial pulse" of the HM3 is detectable in the macro- and microcirculation but without creating a significant alteration in PI compared with HMII patients. Increased transmission of pulsatility and the association between pump speed and PI in the microcirculation indicate that the future clinical care of HM3 patients may involve individualized pump settings according to the microcirculatory PI in specific end-organs.

Scleral Thickness in Autosomal Dominant Best Vitelliform Macular Dystrophy.

PURPOSE: To investigate the posterior and equatorial scleral thickness in patients with autosomal dominant Best disease, a condition that has chronic subretinal fluid. METHODS: Retrospective study involving patients with Best disease and age-matched controls. Participants were evaluated with contact B-scan ultrasonography and enhanced depth imaging optical coherence tomography to evaluate scleral thickness in the posterior pole and equator. Univariate analysis and generalized estimating equations were used. RESULTS: Of 9 patients with genetically proven Best disease and 23 age-matched controls, there was no significant difference in the age or the gender proportion between groups. Subfoveal choroidal thickness and axial length were not significantly different between groups. Both posterior scleral (OD; 1.38mm vs. 0.89mm, P<.001 and OS; 1.39mm vs. 0.83mm, P<.001) and equatorial scleral (OD; 0.61mm vs. 0.42mm, P=.003, and OS; 0.55mm vs. 0.41mm, P=.017) thicknesses were much greater in cases as compared with controls. Multivariate analysis showed male sex and having Best disease were each significant predictors of posterior scleral thickness and Best disease was the sole significant predictor for equatorial scleral thickness. CONCLUSION: BEST1 gene may have a developmental role leading to having a thicker sclera, influencing disease manifestation, and contributing to the accumulation of subretinal fluid in Best disease.

Principles of Ophthalmic Ultrasound.

Introduction: Ultrasound imaging of the eye was introduced over 50 years ago. While the physical principles of ultrasound imaging have not changed, technology has undergone tremendous and ongoing development. Areas covered: The fundamentals of ultrasound physics, biometry (A-scan), structural imaging (B-scan) and blood-flow imaging and measurement (Doppler) will be described. Emphasis will be placed on technological development and potential future advances. Expert opinion: While A- and B-scan ultrasound of the eye has traditionally been performed with focused single-element transducers, the introduction of annular and linear arrays has enhanced clinical utility. Future advances, especially in multielement arrays, and point-of-care systems promise amazing new capabilities for diagnostic imaging of the eye and orbit.

Automated Classification and Detection of Staphyloma with Ultrasound Images in Pathologic Myopia Eyes.

The aim of this study was to develop an eyewall curvature- and axial length (AxL)-based algorithm to automate detection (clinician-free) of staphyloma ridge and apex locations using ultrasound (US). Forty-six individuals (with emmetropia, high myopia or pathologic myopia) were enrolled in this study (AxL range: 22.3-39.3 mm), yielding 130 images in total. An intensity-based segmentation algorithm automatically tracked the posterior eyewall, calculating the posterior eyewall local curvature (K) and distance (L) to the transducer and the location of the staphyloma apex. By use of the area under the receiver operator characteristic (AUROC) curve to evaluate the diagnostic ability of eight local statistics derived from K, L and AxL, the algorithm successfully quantified non-uniformity of eye shape with an AUROC > 0.70 for most K-based parameters. The performance of binary classification (staphyloma absence vs. presence) was assessed with the best classifier (the combination of AxL, standard deviation of K and standard deviation of L) yielding a diagnostic validation performance of 0.897, which was comparable to the diagnostic performance of junior clinicians. The staphyloma apex was localized with an average error of 1.35 ± 1.34 mm. Combined with the real-time data acquisition capabilities of US, this method can be employed as a screening tool for clinician-free in vivo staphyloma detection.

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 Ultrasound: Review of Bioeffects and Safety, Including Fetal and Point of Care Perspective: Review of Bioeffects and Safety, Including Fetal and Point-of-Care Perspective.

Ocular ultrasound is an invaluable tool for the evaluation of the eye and orbit. However, the eye and orbit are potentially sensitive to the thermal and mechanical effects of ultrasound. When performing B-mode imaging, dedicated ocular settings should be used. If these settings are not available, limiting the acoustic output to Food and Drug Administration (FDA) recommended maximum levels is strongly advised. Especially important is the acoustic output in spectral (pulsed) and color Doppler modes, which can exceed the FDA's maximum recommended levels for the eye. Adjusting settings to decrease acoustic output and limiting the time of the examination should be done when performing a Doppler examination. The acoustic output of shear wave elastography is significantly higher than FDA guidelines for the eye and should be considered experimental.

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.

Ultrasonographic Visualization of Bilaterally Fused Eyelids in a Premature Neonate.

In cases of significant prematurity, neonates born with eyelid fusion can undergo spontaneous eyelid disjunction. Here, the authors present such a case, along with ultrasound findings shortly before eyelid separation. All protected patient information extracted for this report was done so in accordance with the Health Insurance Portability and Accountability Act. This report was prepared in accordance with the tenants of the Declaration of Helsinki.

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.

High-Frequency Multipulse, Plane-Wave Acoustic Contrast Imaging.

Multipulse (MP) ultrasound contrast agent (UCA) imaging is a method to increase the contrast-to-background (CBR) ratio in regions of blood flow. Plane-wave imaging allows high frame rates, and with high-frequency ultrasound, fine-spatial and temporal resolution. MP and plane-wave imaging have not been applied to high-frequency ultrasound. Here, an 18-MHz linear array was employed to implement the MP methods of pulse inversion (PI) and amplitude modulation (AM) using high-speed, multiangle, compound plane-wave imaging. A flow of the UCA DEFINITY© at a dilution ratio of 2000:1 circulating through a 2-mm-diameter flow channel in a tissue-mimicking phantom was used to characterize CBR and compared with cases of standard, multiangle compound plane-wave imaging. The relative improvement of PI and AM versus standard plane-wave imaging ranged from 5 to 10 dB. The CBR was observed to be stable over a 60-min time duration for a 2000:1 dilution ratio and a 2000:1 dilution ratio provided an optimal CBR.

Assessment of Vitreous Structure and Visual Function after Neodymium:Yttrium-Aluminum-Garnet Laser Vitreolysis.

PURPOSE: Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision. DESIGN: Retrospective, comparative study. PARTICIPANTS: One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation. METHODS: The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision. MAIN OUTCOME MEASURES: Results of NEI-VFQ-39, QUS, BCVA, and CSF. RESULTS: Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings. CONCLUSIONS: As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

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.

Treatment of Macular Degeneration with Sildenafil: Results of a Two-Year Trial.

OBJECTIVE: To evaluate PDE5/6 inhibition with sildenafil to reduce choroidal ischemia and treat age-related macular degeneration. METHODS: Sildenafil was prescribed to treat participants with macular degenerations or macular dystrophies measured by spectral-domain optical coherence tomography, color fundus photography, enhanced depth imaging, and best-corrected visual acuity. RESULTS: No change in calcified drusen was noted. Vitelliform-type soft drusen were not substantially changed. A participant with Best vitelliform macular dystrophy had a significant improvement in vision as well as in photoreceptor and ellipsoid layers. CONCLUSIONS: Our research supports sildenafil as a safe treatment for age-related and vitelliform macular degenerations. Thickened Bruch's membrane reduces the beneficial effect of perfusion increase, but all eyes appear to benefit from PDE6. Notably, maintenance or improvement in the photoreceptor layer may be the most significant result of sildenafil and is consistent with PDE6 inhibition. Thus, sil-denafil treatment of macular degeneration offers significant potential for vision retention and recovery.