Association between Visual Acuity and Retinal Layer Metrics in Diabetics with and without Macular Edema.

PURPOSE: Diabetes is known to cause alterations in retinal microvasculature and tissue that progressively lead to visual impairment. Optical coherence tomography (OCT) is useful for assessment of total retinal thickening due to diabetic macular edema (DME). In the current study, we determined associations between visual acuity (VA) and retinal layer thickness, reflectance, and interface disruption derived from enface OCT images in subjects with and without DME. MATERIALS AND METHODS: Best corrected VA was measured and high-density OCT volume scans were acquired in 149 diabetic subjects. A previously established image segmentation method identified retinal layer interfaces and locations of visually indiscernible (disrupted) interfaces. Enface thickness maps and reflectance images of the nerve fiber layer (NFL), combined ganglion cell and inner plexiform layer (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE) were generated in the central macular subfield. The associations among VA and retinal layer metrics were determined by multivariate linear regressions after adjusting for covariates (age, sex, race, HbA1c, diabetes type, and duration) and correcting for multiple comparisons. RESULTS: In DME subjects, increased GCLIPL and OPL thickness and decreased OSL thickness were associated with reduced VA. Furthermore, increased NFL reflectance and decreased OSL reflectance were associated with reduced VA. Additionally, increased areas of INL and ONL interface disruptions were associated with reduced VA. In subjects without DME, increased INL thickness was associated with reduced VA, whereas in subjects without DME but with previous antivascular endothelium growth factor treatment, thickening of OPL was associated with reduced VA. CONCLUSIONS: Alterations in retinal layer thickness and reflectance metrics derived from enface OCT images were associated with reduced VA with and without presence of DME, suggestive of their potential for monitoring development, progression, and treatment of DME.

Retinal tissue oxygen tension and consumption during light flicker stimulation in rat.

Light flicker stimulation has been shown to increase inner retinal oxygen metabolism and supply. The purpose of the study was to test the hypothesis that sustained light flicker stimulation of various durations alters the depth profile metrics of oxygen partial pressure in the retinal tissue (tPO2) but not the outer retinal oxygen consumption rate (QO2). In 17 rats, tPO2 depth profiles were derived by phosphorescence lifetime imaging after intravitreal injection of an oxyphor. tPO2 profile metrics, including mean inner retinal tPO2, maximum outer retinal tPO2 and minimum outer retinal tPO2 were determined. QO2 was calculated using a one-dimensional oxygen diffusion model. Data were acquired at baseline (constant light illumination) and during light flicker stimulation at 10 Hz under the same mean illumination levels, and differences between values obtained during flicker and baseline were calculated. None of the tPO2 profile metrics or QO2 differences depended on the duration of light flicker stimulation (R2 ≤ 0.03). No significant change in any of the tPO2 profile metrics was detected with light flicker compared with constant light (P ≥ 0.08). Light flicker decreased QO2 from 0.53 ±â€¯0.29 to 0.38 ±â€¯0.30 mL O2/(min*100 gm), a reduction of 28% (P = 0.02). The retinal compensatory responses to the physiologic challenge of light flicker stimulation were effective in maintaining the levels of oxygen at or near baseline in the inner retina. Oxygen availability to the inner retina during light flicker may also have been enhanced by the decrease in QO2.

Assessment of Global and Local Alterations in Retinal Layer Thickness in Ins2 (Akita) Diabetic Mice by Spectral Domain Optical Coherence Tomography.

PURPOSE/AIM: The Ins2 (Akita) mouse is a spontaneous diabetic mouse model with a heterozygous mutation in the insulin 2 gene that results in sustained hyperglycemia. The purpose of the study was to assess global and local retinal layer thickness alterations in Akita mice by analysis of spectral domain optical coherence tomography (SD-OCT) images. MATERIALS AND METHODS: SD-OCT imaging was performed in Akita and wild-type mice at 12 and 24 weeks of age. Inner retinal thickness (IRT), outer retinal thickness (ORT), total retinal thickness (TRT), and photoreceptor outer segment length (OSL) were measured. Mean global thickness values were compared between Akita and wild-type mice. Local thickness variations in Akita mice were assessed based on normative values in wild-type mice. RESULTS: Akita mice had higher blood glucose levels and lower body weights (p < 0.001). On average, IRT, ORT, and TRT were approximately 2% lower in Akita mice than in wild-type mice (p ≤ 0.02). In Akita mice, the percent difference between retinal areas with thickness below and above normative values for IRT, ORT, and TRT was 22%, 32%, and 38%, respectively. CONCLUSIONS: These findings support the use of the Akita mouse model to study the retinal neurodegenerative effects of hyperglycemia.

A method for volumetric retinal tissue oxygen tension imaging.

PURPOSE: Inadequate retinal oxygenation occurs in many vision-threatening retinal diseases, including diabetic retinopathy, retinal vascular occlusions, and age-related macular degeneration. Therefore, techniques that assess retinal oxygenation are necessary to understand retinal physiology in health and disease. The purpose of the current study is to report a method for the three-dimensional (3D) imaging of retinal tissue oxygen tension (tPO2) in rats. METHODS: Imaging was performed in Long Evans pigmented rats under systemic normoxia (N = 6) or hypoxia (N = 3). A vertical laser line was horizontally scanned on the retina and a series of optical section phase-delayed phosphorescence images were acquired. From these images, phosphorescence volumes at each phase delay were constructed and a 3D retinal tPO2 volume was generated. Retinal tPO2 volumes were quantitatively analyzed by generating retinal depth profiles of mean tPO2 (MtPO2) and the spatial variation of tPO2 (SVtPO2). The effects of systemic condition (normoxia/hypoxia) and retinal depth on MtPO2 and SVtPO2 were determined by mixed linear model. RESULTS: Each 3D retinal tPO2 volume was approximately 500 × 750 × 200 µm (horizontal × vertical × depth) and consisted of 45 en face tPO2 images through the retinal depth. MtPO2 at the chorioretinal interface was significantly correlated with systemic arterial oxygen tension (P = 0.007; N = 9). There were significant effects of both systemic condition and retinal depth on MtPO2 and SVtPO2, such that both were lower under hypoxia than normoxia and higher in the outer retina than inner retina (P < 0.001). CONCLUSION: For the first time, 3D imaging of retinal tPO2 was demonstrated, with potential future application for assessment of physiological alterations in animal models of retinal diseases.

Retinal Vascular and Oxygen Temporal Dynamic Responses to Light Flicker in Humans.

Purpose: To mathematically model the temporal dynamic responses of retinal vessel diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF) to light flicker and to describe their responses to its cessation in humans. Methods: In 16 healthy subjects (age: 60 ± 12 years), retinal oximetry was performed before, during, and after light flicker stimulation. At each time point, five metrics were measured: retinal arterial and venous D (DA, DV) and SO2 (SO2A, SO2V), and OEF. Intra- and intersubject variability of metrics was assessed by coefficient of variation of measurements before flicker within and among subjects, respectively. Metrics during flicker were modeled by exponential functions to determine the flicker-induced steady state metric values and the time constants of changes. Metrics after the cessation of flicker were compared to those before flicker. Results: Intra- and intersubject variability for all metrics were less than 6% and 16%, respectively. At the flicker-induced steady state, DA and DV increased by 5%, SO2V increased by 7%, and OEF decreased by 13%. The time constants of DA and DV (14, 15 seconds) were twofold smaller than those of SO2V and OEF (39, 34 seconds). Within 26 seconds after the cessation of flicker, all metrics were not significantly different from before flicker values (P ≥ 0.07). Conclusions: Mathematical modeling revealed considerable differences in the time courses of changes among metrics during flicker, indicating flicker duration should be considered separately for each metric. Future application of this method may be useful to elucidate alterations in temporal dynamic responses to light flicker due to retinal diseases.

Retinal Oximetry and Vessel Diameter Measurements With a Commercially Available Scanning Laser Ophthalmoscope in Diabetic Retinopathy.

Purpose: To test the hypothesis that retinal vascular diameter and hemoglobin oxygen saturation alterations, according to stages of diabetic retinopathy (DR), are discernible with a commercially available scanning laser ophthalmoscope (SLO). Methods: One hundred eighty-one subjects with no diabetes (No DM), diabetes with no DR (No DR), nonproliferative DR (NPDR), or proliferative DR (PDR, all had photocoagulation) underwent imaging with an SLO with dual lasers (532 nm and 633 nm). Customized image analysis software determined the diameters of retinal arteries and veins (DA and DV) and central retinal artery and vein equivalents (CRAE and CRVE). Oxygen saturations of hemoglobin in arteries and veins (SO2A and SO2V) were estimated from optical densities of vessels on images at the two wavelengths. Statistical models were generated by adjusting for effects of sex, race, age, eye, and fundus pigmentation. Results: DA, CRAE, and CRVE were reduced in PDR compared to No DM (P ≤ 0.03). DV and CRVE were similar between No DM and No DR, but they were higher in NPDR than No DR (P ≤ 0.01). Effect of stage of disease on SO2A differed by race, being increased relative to No DM in NPDR and PDR in Hispanic participants only (P ≤ 0.02). Relative to No DM, SO2V was increased in NPDR and PDR (P ≤ 0.05). Conclusions: Alterations in retinal vascular diameters and SO2 by diabetic retinopathy stage can be detected with a widely available SLO, and covariates such as race can influence the results.

A Method for Combined Retinal Vascular and Tissue Oxygen Tension Imaging.

The retina requires adequate oxygenation to maintain cellular metabolism and visual function. Inner retinal oxygen metabolism is directly related to retinal vascular oxygen tension (PO2) and inner retinal oxygen extraction fraction (OEF), whereas outer retinal oxygen consumption (QO2) relies on oxygen availability by the choroid and is contingent upon retinal tissue oxygen tension (tPO2) gradients across the retinal depth. Thus far, these oxygenation and metabolic parameters have been measured independently by different techniques in separate animals, precluding a comprehensive and correlative assessment of retinal oxygenation and metabolism dynamics. The purpose of the current study is to report an innovative optical system for dual oxyphor phosphorescence lifetime imaging to near-simultaneously measure retinal vascular PO2 and tPO2 in rats. The use of a new oxyphor with different spectral characteristics allowed differentiation of phosphorescence signals from the retinal vasculature and tissue. Concurrent measurements of retinal arterial and venous PO 2 , tPO2 through the retinal depth, inner retinal OEF, and outer retinal QO 2 were demonstrated, permitting a correlative assessment of retinal oxygenation and metabolism. Future application of this method can be used to investigate the relations among retinal oxygen content, extraction and metabolism under pathologic conditions and thus advance knowledge of retinal hypoxia pathophysiology.

Assessment of Conjunctival Microvascular Hemodynamics in Stages of Diabetic Microvasculopathy.

Diabetes impairs the microcirculation and function of various vital tissues throughout the body. The conjunctival microcirculation can be non-invasively imaged and thus enables assessment of microvascular hemodynamics. In this study, alterations in conjunctival microvascular hemodynamics were quantitatively assessed at stages of increasing diabetic microvasculopathy based on diabetic retinopathy (DR). Subjects were categorized into non-diabetic control (C, N = 34), no clinically visible DR (NDR, N = 47), non-proliferative DR (NPDR, N = 45), and proliferative DR (PDR, N = 35). Conjunctival hemodynamic descriptors, namely vessel diameter (D), blood velocity (V), blood flow (Q), wall shear rate (WSR), and wall shear stress (WSS) were measured in arterioles and venules, and compared between DR and C subjects using generalized linear mixed models. In arterioles, V, WSR, and WSS were lower in NDR (P ≤ 0.01). V was lower in NDR than NPDR and PDR subjects (P ≤ 0.02). In venules, D was higher in NDR and NPDR (P ≤ 0.03), while V was lower in PDR (P = 0.04). Venular V and Q were higher in NPDR than PDR subjects (P ≤ 0.04). WSR and WSS were lower in all stages of DR (P ≤ 0.05), suggestive of the potential of WSS as a marker of diabetic microvasculopathy. Quantitative assessment of conjunctival hemodynamics can potentially be useful for evaluation of diabetic microvasculopathy.

Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2Akita Diabetic Mice.

PURPOSE: Retinal nonperfusion and hypoxia are important factors in human diabetic retinopathy, and these presumably inhibit energy production and lead to cell death. The purpose of this study was to elucidate the effect of diabetes on inner retinal oxygen delivery and metabolism in a mouse model of diabetes. METHODS: Phosphorescence lifetime and blood flow imaging were performed in spontaneously diabetic Ins2Akita (n = 22) and nondiabetic (n = 22) mice at 12 and 24 weeks of age to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). Inner retinal oxygen delivery (DO2) and metabolism (MO2) were calculated as F ∗ O2A and F ∗ (O2A - O2V), respectively. Oxygen extraction fraction (OEF), which equals MO2/DO2, was calculated. RESULTS: DO2 at 12 weeks were 112 ± 40 and 97 ± 29 nL O2/min in nondiabetic and diabetic mice, respectively (NS), and 148 ± 31 and 85 ± 37 nL O2/min at 24 weeks, respectively (P < 0.001). MO2 were 65 ± 31 and 66 ± 27 nL O2/min in nondiabetic and diabetic mice at 12 weeks, respectively, and 79 ± 14 and 54 ± 28 nL O2/min at 24 weeks, respectively (main effects = NS). At 12 weeks OEF were 0.57 ± 0.17 and 0.67 ± 0.09 in nondiabetic and diabetic mice, respectively, and 0.54 ± 0.07 and 0.63 ± 0.08 at 24 weeks, respectively (main effect of diabetes: P < 0.01). CONCLUSIONS: Inner retinal MO2 was maintained in diabetic Akita mice indicating that elevation of the OEF adequately compensated for reduced DO2 and prevented oxidative metabolism from being limited by hypoxia.

The Effects of Diabetic Retinopathy Stage and Light Flicker on Inner Retinal Oxygen Extraction Fraction.

PURPOSE: We determined the effects of light flicker and diabetic retinopathy (DR) stage on retinal vascular diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF). METHODS: Subjects were categorized as nondiabetic control (NC, n = 42), diabetic with no clinical DR (NDR; n = 32), nonproliferative DR (NPDR; n = 42), or proliferative DR (PDR; n = 14). Our customized optical imaging system simultaneously measured arterial and venous D (DA, DV) and SO2 (SO2A, SO2V) before and during light flicker. Inner retinal OEF was derived from SO2 values. Light flicker-induced ratios of metrics (DAR, DVR, SO2AR, SO2VR, OEFR) were calculated. RESULTS: Arterial D was larger in NPDR compared to NC (P = 0.01) and PDR (P = 0.002), whereas DV was similar among groups (P ≥ 0.16). Light flicker increased DA and DV (P ≤ 0.004), but DAR and DVR were similar among groups (P ≥ 0.09). Arterial SO2 was higher in all groups compared to NC (P ≤ 0.02) and higher in PDR compared to NDR and NPDR (P<0.001). Arterial SO2 did not change with light flicker (P ≥ 0.1). Venous SO2 was higher in NPDR and PDR compared to NC and NDR (P ≤ 0.02). Light flicker increased SO2V in NC, NDR, and PDR (P ≤ 0.003), and SO2VR was lower in NPDR compared to NC and NDR (P ≤ 0.05). Inner retinal OEF was lower in NPDR compared to NDR and PDR (P ≤ 0.02). Light flicker decreased OEF (P ≤ 0.03), but OEFR was greater in NPDR compared to NC and NDR (P ≤ 0.03). CONCLUSIONS: The findings of alterations in retinal D, SO2, OEF, and their light flicker-induced responses at stages of DR may be useful to elucidate the pathophysiology of DR.

Alterations in Retinal Layer Thickness and Reflectance at Different Stages of Diabetic Retinopathy by En Face Optical Coherence Tomography.

PURPOSE: This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR). METHODS: High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer. RESULTS: En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R ≤-0.31; P ≤ 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P< 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL. CONCLUSIONS: Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR.

Automated Real-Time Conjunctival Microvasculature Image Stabilization.

The bulbar conjunctiva is a thin, vascularized membrane covering the sclera of the eye. Non-invasive imaging techniques have been utilized to assess the conjunctival vasculature as a means of studying microcirculatory hemodynamics. However, eye motion often confounds quantification of these hemodynamic properties. In the current study, we present a novel optical imaging system for automated stabilization of conjunctival microvasculature images by real-time eye motion tracking and realignment of the optical path. The ability of the system to stabilize conjunctival images acquired over time by reducing image displacements and maintaining the imaging area was demonstrated.

The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats.

Vascular endothelial growth factor (VEGF) is stimulated by hypoxia and plays an important role in pathologic vascular leakage and neovascularization. Increased VEGF may affect inner retinal oxygen delivery (DO2) and oxygen metabolism (MO2), however, quantitative information is lacking. We tested the hypotheses that VEGF increases DO2, but does not alter MO2. In 10 rats, VEGF was injected intravitreally into one eye, whereas balanced salt solution (BSS) was injected into the fellow eye, 24 h prior to imaging. Vessel diameters and blood velocities were determined by red-free and fluorescent microsphere imaging, respectively. Vascular PO2 values were derived by phosphorescence lifetime imaging of an intravascular oxyphor. Retinal blood flow, vascular oxygen content, DO2 and MO2 were calculated. Retinal arterial and venous diameters were larger in VEGF-injected eyes compared to control eyes (P < 0.03), however no significant difference was observed in blood velocity (P = 0.21). Thus, retinal blood flow was greater in VEGF-injected eyes (P = 0.007). Retinal vascular PO2 and oxygen content were similar between control and VEGF-injected eyes (P > 0.11), while the arteriovenous oxygen content difference was marginally lower in VEGF-injected eyes (P = 0.05). DO2 was 950 ± 340 and 1380 ± 650 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.005). MO2 was 440 ± 150 and 490 ± 190 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.31). Intravitreally administered VEGF did not alter MO2 but increased DO2, suggesting VEGF may play an offsetting role in conditions characterized by retinal hypoxia.

Automated Assessment of Hemodynamics in the Conjunctival Microvasculature Network.

The conjunctival microcirculation is accessible for direct visualization and quantitative assessment of microvascular hemodynamic properties. Currently available methods to assess hemodynamics in the conjunctival microvasculature use manual or semi-automated algorithms, which can be inefficient for application to a large number of microvessels within the microvascular network. We present an automated image analysis method for measurements of diameter and blood velocity in microvessels. The method was applied to conjunctival microcirculation images acquired in 15 healthy human subjects. Frangi filtering, thresholding, and morphological closing were applied to automatically segment microvessels, while variance filtering was used to detect blood flow. Diameter and blood velocity were measured in arterioles and venules within the conjunctival microvascular network, and blood flow and wall shear rate were calculated. Repeatability and validity of hemodynamic measurements were established. The automated image analysis method allows reliable, rapid and quantitative assessment of hemodynamics in the conjunctival microvascular network and can be potentially applied to microcirculation images of other tissues.

Enface Thickness Mapping and Reflectance Imaging of Retinal Layers in Diabetic Retinopathy.

PURPOSE: To present a method for image segmentation and generation of enface thickness maps and reflectance images of retinal layers in healthy and diabetic retinopathy (DR) subjects. METHODS: High density spectral domain optical coherence tomography (SDOCT) images were acquired in 10 healthy and 4 DR subjects. Customized image analysis software identified 5 retinal cell layer interfaces and generated thickness maps and reflectance images of the total retina (TR), inner retina (IR), outer retina (OR), and the inner segment ellipsoid (ISe) band. Thickness maps in DR subjects were compared to those of healthy subjects by generating deviation maps which displayed retinal locations with thickness below, within, and above the normal 95% confidence interval. RESULTS: In healthy subjects, TR and IR thickness maps displayed the foveal depression and increased thickness in the parafoveal region. OR and ISe thickness maps showed increased thickness at the fovea, consistent with normal retinal anatomy. In DR subjects, thickening and thinning in localized regions were demonstrated on TR, IR, OR, and ISe thickness maps, corresponding to retinal edema and atrophy, respectively. TR and OR reflectance images showed reduced reflectivity in regions of increased thickness. Hard exudates appeared as hyper-reflective spots in IR reflectance images and casted shadows on the deeper OR and ISe reflectance images. The ISe reflectance image clearly showed the presence of focal laser scars. CONCLUSIONS: Enface thickness mapping and reflectance imaging of retinal layers is a potentially useful method for quantifying the spatial and axial extent of pathologies due to DR.

Inner Retinal Oxygen Extraction Fraction in Response to Light Flicker Stimulation in Humans.

PURPOSE: Light flicker has been shown to stimulate retinal neural activity, increase blood flow, and alter inner retinal oxygen metabolism (MO2) and delivery (DO2). The purpose of the study was to determine the change in MO2 relative to DO2 due to light flicker stimulation in humans, as assessed by the inner retinal oxygen extraction fraction (OEF). METHODS: An optical imaging system, based on a modified slit lamp biomicroscope, was developed for simultaneous measurements of retinal vascular diameter (D) and oxygen saturation (SO2). Retinal images were acquired in 20 healthy subjects before and during light flicker stimulation. Arterial and venous D (DA and DV) and SO2 (SO2A and SO2V) were quantified within a circumpapillary region. Oxygen extraction fraction was defined as the ratio of MO2 to DO2 and was calculated as (SO2A - SO2V)/SO2A. Reproducibility of measurements was assessed. RESULTS: Coefficients of variation and intraclass correlation coefficients of repeated measurements were <5% and ≥0.83, respectively. During light flicker stimulation, DA, DV , and SO2V significantly increased (P ≤ 0.004). Oxygen extraction fraction was 0.37 ± 0.08 before light flicker and significantly decreased to 0.31 ± 0.07 during light flicker (P = 0.001). CONCLUSIONS: Oxygen extraction fraction before and during light flicker stimulation is reported in human subjects for the first time. Oxygen extraction fraction decreased during light flicker stimulation, indicating the change in DO2 exceeded that of MO2. This technology is potentially useful for the detection of changes in OEF response to light flicker in physiological and pathological retinal conditions.

Conjunctival microvascular hemodynamics following vaso-occlusive crisis in sickle cell disease.

Painful vaso-occlusive crisis (VOC) is the clinical hallmark of sickle cell disease (SCD). Microcirculatory hemodynamic changes following painful VOC may be indicative of future development of VOC events in subjects with SCD. The purpose of the present study was to determine alterations in conjunctival microvascular hemodynamics during non-crisis state in SCD subjects with a history of VOC. Conjunctival microcirculation imaging was performed to measure conjunctival diameter (D) and axial blood velocity (V) in 10 control and 30 SCD subjects. SCD subjects were categorized into two groups based on their history of VOC within a 2-year period before imaging (with or without VOC-H) and also based on whether there was progression in the rate of VOCs during a 2-year period following imaging as compared to before imaging (with or without VOC-P). Conjunctival V was significantly higher in SCD subjects with VOC-H than in both control subjects and SCD subjects without VOC-H (P≤0.03). Conjunctival V was also significantly higher in SCD subjects with VOC-P compared with control subjects and SCD subjects without VOC-P (P≤0.03). Assessment of the conjunctival microcirculation may be useful for understanding hemodynamic changes that lead to VOC events in SCD subjects.

Changes in Conjunctival Hemodynamics Predict Albuminuria in Sickle Cell Nephropathy.

BACKGROUND: Albuminuria is an early manifestation of deterioration in renal function in subjects with sickle cell disease (SCD). Hyperfiltration may be an early mechanism for kidney damage in SCD. The purpose of the current study was to determine the association between conjunctival hemodynamics and albuminuria in SCD subjects with preserved glomerular filtration rate. METHODS: Conjunctival microcirculation imaging was performed to measure conjunctival diameter and axial blood velocity (V) in 35 SCD and 10 healthy control subjects. Albuminuria, defined as albumin excretion ratio (AER), was obtained from the medical charts. Based on the 95% CI of conjunctival V in control subjects (0.40-0.60 mm/s), SCD subjects were allocated to 3 groups: V1 <0.40 mm/s (n = 7), V2 of 0.40-0.60 mm/s (n = 18) and V3 ≥0.60 mm/s (n = 10). RESULTS: Mean log(AER) measurements in the V1, V2 and V3 groups were 1.08 ± 0.67, 1.39 ± 0.59 and 2.00 ± 0.91 mg/g creatinine, respectively, and followed a positive linear trend from the V1 to V3 groups (p = 0.01). By multivariate linear regression analysis, conjunctival V significantly correlated with albuminuria (p = 0.01) independent of age, blood pressure, α-thalassemia, hematocrit, white blood cell count and lactate dehydrogenase concentration. CONCLUSIONS: Increased conjunctival V is associated with albuminuria in SCD subjects. Assessment of conjunctival microvascular hemodynamics may improve our understanding of the pathophysiology and clinical management of sickle cell nephropathy.

Feasibility of level-set analysis of enface OCT retinal images in diabetic retinopathy.

Pathology segmentation in retinal images of patients with diabetic retinopathy is important to help better understand disease processes. We propose an automated level-set method with Fourier descriptor-based shape priors. A cost function measures the difference between the current and expected output. We applied our method to enface images generated for seven retinal layers and determined correspondence of pathologies between retinal layers. We compared our method to a distance-regularized level set method and show the advantages of using well-defined shape priors. Results obtained allow us to observe pathologies across multiple layers and to obtain metrics that measure the co-localization of pathologies in different layers.

Feasibility of assessment of conjunctival microvascular hemodynamics in unilateral ischemic stroke.

Since the internal carotid artery supplies blood to both the eye and the brain, ocular microvascular hemodynamics can be altered due to ischemic stroke. The purpose of the current study was to establish the feasibility of conjunctival microcirculation imaging for detection of inter-ocular differences in microvascular hemodynamics in subjects with unilateral ischemic stroke. Conjunctival microcirculation imaging was performed in both eyes of 15 healthy control subjects and 12 subjects following unilateral ischemic stroke. Diameter and axial blood velocity were measured in multiple conjunctival venules of each eye. A two-way repeated measures analysis of variance was performed to determine the effects of stroke (control vs. stroke) and side of stroke (ipsilateral vs. contralateral) on conjunctival diameter and axial blood velocity. There was no significant main effect of stroke on conjunctival diameter (P=0.7) or conjunctival axial blood velocity (P=0.9). There was no significant main effect of side of stroke on conjunctival diameter (P=0.8), but there was a significant main effect of side of stroke on conjunctival axial blood velocity (P=0.02). There was a significant interaction effect between stroke and side of stroke (P=0.04), indicating that conjunctival axial blood velocity was lower in ipsilateral eyes than in contralateral eyes of stroke subjects. Conjunctival axial blood velocity and internal carotid artery blood velocity were correlated in stroke subjects (r=0.75, P=0.01, N=10). Conjunctival microcirculation imaging is a feasible method to detect inter-ocular differences in microvascular hemodynamics in subjects with unilateral ischemic stroke.