Alterations in retinal pulse wave velocity under experimental ocular hypertension.

Impairments of blood flow and autoregulation have been implicated in diabetic retinopathy and glaucoma. Thus, identifying biomarkers of retinal vascular compliance and regulatory capacity is of potential value for understanding the pathophysiology and evaluating onset or progression of disease. Pulse wave velocity (PWV) represents the speed of the pulse-propagated pressure wave within blood vessels and has shown promise as a marker of vascular compliance. The purpose of the current study was to report a method for comprehensive assessment of retinal PWV based on spectral analysis of pulsatile intravascular intensity waveforms and determine alterations due to experimental ocular hypertension. Retinal PWV was linearly related to vessel diameter. Increased retinal PWV was associated with elevated intraocular pressure. Retinal PWV has the potential to serve as a vasoregulation biomarker for investigating vascular factors that contribute to the development of retinal diseases in animal models.

The accumulated oxygen deficit as an indicator of the ischemic retinal insult.

We here attempt to improve quantification of the ischemic retinal insult, that is, what is imposed on the retinal tissue by ischemia, especially in experimental models of ischemia. The ischemic retinal insult initiates the ischemic retinal injury (or outcome). Accordingly, it is reasonable to assume that the better the quantification of the insult, the better the correlation with, and thereby estimation of, the injury. The insult seldom has been quantified in terms of the relevant physiological factors, especially in connection with the rate of oxygen delivery (DO2). We here propose the accumulated oxygen deficit (AO2D) as an indicator of the ischemic retinal insult. We hypothesized that AO2D is correlated with the rate of oxygen metabolism measured 1 h after reperfusion following an episode of ischemia (MO2_1_Hr). Previously, we showed that MO2_1_Hr is related to the electroretinogram amplitude and the retinal thickness when they are measured seven days after reperfusion. We studied 27 rats, as well as 26 rats from our published data on retinal ischemia in which we had measurements of DO2 and duration of ischemia (T) of various levels and durations. We also measured DO2 in 29 rats treated with sham surgery. Ischemia was induced by either ipsilateral or bilateral common carotid artery occlusion or by ophthalmic artery occlusion, which gave a wide range of DO2. DO2 and MO2_1_Hr were evaluated based on three types of images: 1) red-free images to measure vessel diameters, 2) fluorescence images to estimate blood velocities by the displacement of intravascular fluorescent microspheres over time, and 3) phosphorescence images to quantify vascular oxygen tension from the phosphorescence lifetime of an intravascular oxygen sensitive phosphor. Loss of oxygen delivery (DO2L) was calculated as the difference between DO2 under normal/sham condition and DO2 during ischemia. AO2D, a volume of oxygen, was calculated as the product DO2L and T. Including all data, the linear relationship between AO2D and MO2_1_Hr was significant (R2 = 0.261, P = 0.0003). Limiting data to that in which T or DO2L was maximal also yielded significant relationships, and revealed that DO2L at a long duration of ischemia contributed disproportionately more than T to MO2_1_Hr. We discuss the potential of AO2D for quantifying the ischemic retinal insult, predicting the ischemic retinal injury and evaluating the likelihood of infarction.

Impairments of retinal hemodynamics and oxygen metrics in ocular hypertension-induced ischemia-reperfusion.

Ischemia-reperfusion (I/R) is an established model for retinal neurodegeneration. However, there is limited knowledge of retinal physiological metrics and their relationships to retinal function and morphology in the I/R model. The purpose of the study was to test the hypotheses that retinal hemodynamic and oxygen metrics are impaired and associated with visual dysfunction, retinal thinning, and retinal ganglion cell (RGC) loss due to I/R injury. Intraocular pressure (IOP) was increased in one eye of 10 rats for 90 min followed by reperfusion. Fellow eyes served as controls. After one week of reperfusion, multimodal imaging was performed to quantify total retinal blood flow (TRBF) and retinal vascular oxygen contents. Retinal oxygen delivery (DO2) and metabolism (MO2) were calculated. Pattern-evoked electroretinography (PERG) and optical coherence tomography were performed to measure RGC function and retinal thicknesses, respectively. RGCs were counted from retina whole mounts. After one week of reperfusion, TRBF was lower in study eyes than in control eyes (p < 0.0003). Similarly, DO2 and MO2 were reduced in study eyes compared to control eyes (p < 0.003). PERG amplitude, TRT, IRT, ORT, and RGCs were also lower in study eyes (p ≤ 0.01). DO2 and MO2 were correlated with PERG amplitude, TRT, IRT, and ORT (r ≥ 0.6, p ≤ 0.005). The findings improve knowledge of physiological metrics affected by I/R injury and have the potential for identifying biomarkers of injury and outcomes for evaluating experimental treatments.

Assessment of retinal oxygen metabolism, visual function, thickness and degeneration markers after variable ischemia/reperfusion in rats.

After total retinal ischemia induced experimentally by ophthalmic vessel occlusion followed by reperfusion, studies have reported alterations in retinal oxygen metabolism (MO2), delivery (DO2), and extraction fraction (OEF), as well as visual dysfunction and cell loss. In the current study, under variable durations of ischemia/reperfusion, changes in these oxygen metrics, visual function, retinal thickness, and degeneration markers (gliosis and apoptosis) were assessed and related. Additionally, the prognostic value of MO2 for predicting visual function and retinal thickness outcomes was reported. Sixty-one rats were divided into 5 groups of ischemia duration (0 [sham], 60, 90, 120, or 180 min) and 2 reperfusion durations (1 h, 7 days). Phosphorescence lifetime and blood flow imaging, electroretinography, and optical coherence tomography were performed. MO2 reduction was related to visual dysfunction, retinal thinning, increased gliosis and apoptosis after 7-days reperfusion. Impairment in MO2 after 1-h reperfusion predicted visual function and retinal thickness outcomes after 7-days reperfusion. Since MO2 can be measured in humans, findings from analogous studies may find value in the clinical setting.

Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration.

The retinal degeneration 1 (rd1) mouse is a well-established model of inherited retinal degeneration, displaying photoreceptor degeneration and retinal vasculature damage. The purpose of the current study was to determine alterations in the rate of oxygen delivery from retinal circulation (DO2), the rate of oxygen extraction from the retinal circulation for metabolism (MO2), and oxygen extraction fraction (OEF) in rd1 mice. The study was performed in a total of 18 wild type (WT) and 10 rd1 mice at both 3-weeks and 12-weeks of age. Retinal arterial and venous oxygen contents (O2A and O2V) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO2 and MO2 were determined as TRBF × O2A and TRBF × (O2A-O2V), respectively. OEF was calculated as MO2/DO2. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO2 and MO2 were lower in rd1 mice compared to WT mice (P ≤ 0.001), whereas OEF was not significantly different between rd1 and WT mice (P = 0.4). TRBF and DO2 were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO2 was not significantly different between age groups (P = 0.4) and OEF was higher at 3-weeks of age compared to 12-weeks of age (P = 0.003). Additionally, the outer and inner retinal cell layer thicknesses were decreased in rd1 mice at 12-weeks of age compared to both age-matched WT mice and rd1 mice at 3-weeks of age (P ≤ 0.02). MO2 was directly correlated with both IR and TR thickness (R ≥ 0.50; P ≤ 0.03, N = 20). The findings indicate that the rate oxygen is supplied by the retinal circulation is decreased and the reduction in oxygen extracted for metabolism is related to retinal cell layer thinning in rd1 mice.

Control of retinal blood flow levels by selected combinations of cervical arterial ligations in rat.

The effect of various combinations of cervical arterial ligations (Combinations) on retinal blood flow (RBF) levels is not known in rats. We hypothesized: 1) No artery exists between the Circle of Willis and the eye, 2) Selective Combinations enable varying RBF levels between normal and zero, 3) In certain Combinations, the capillary bed of the head participates in supplying the eye. Twenty-six Combinations were studied in one eye of 20 Long-Evans rats under general anesthesia. RBF was quantitatively evaluated with our published imaging methods based on direct measurements of venous diameter and blood velocity from the displacement of fluorescent microspheres over time. For each Combination, one or more RBF values (runs) were measured. Data were obtained from 59 runs (2.9 ± 2.7 runs/rat). Levels of RBF ranged from normal to zero. An artery between the Circle of Willis and the eye was excluded. With some Combinations, flow traversed the capillary bed. Combinations were consolidated into five Groups based on the blood flow paths remaining after the ligations. A mixed linear model accounting for multiple measurements in the same eye demonstrated an effect of Group on RBF (P < 0.0005). By major source of ocular blood supply, the trend of RBF levels was: ipsilateral carotid artery > contralateral carotid artery > ipsilateral distal internal carotid artery retrograde from Circle of Willis. The findings advanced knowledge of the sources of blood supply to the rat eye and demonstrated a method of selective cervical arterial ligations for varying RBF levels with potential to impact future retinal ischemia research.

Assessment of retinal vascular oxygenation and morphology at stages of diabetic retinopathy in African Americans.

BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of blindness in working-age adults. The likelihood of visual impairment associated with DR is two-fold higher in the African-American (AA) compared to non-Hispanic white. Although alterations in retinal vessel oxygenation and morphology have been reported in DR, there is limited knowledge about these vascular changes in AA subjects. The purpose of the current study was to investigate alterations in retinal vascular oxygen saturation (SO2), vessel diameter (D) and tortuosity at severity stages of DR in AA subjects. METHODS: A nested case-control study of 56 AA subjects was conducted. Right eyes were grouped as non-diabetic (ND) (N = 26), no clinical DR (NDR) (N = 19), or moderate/severe non-proliferative DR (NPDR) (N = 11). Imaging was performed using a commercially available scanning laser ophthalmoscope. Images were analyzed to determine retinal arterial and venous SO2 (SO2A and SO2V), diameter (DA and DV), and vessel tortuosity index (VTI) (VTIA and VTIV). RESULTS: SO2V and DV were higher in NPDR compared to ND and NDR groups (P < 0.05). There were no significant differences in SO2A and DA among ND, NDR, and NPDR groups (P > 0.8). Maximum VTIA was higher in diabetics (NDR and NPDR) compared to non-diabetics (P < 0.03). There was no significant difference in maximum VTIV among the 3 groups (P = 0.5). CONCLUSIONS: The findings advance our understanding of DR pathophysiology in the AA population and may propel identification of race-specific retinal vascular biomarkers for improved diagnosis and monitoring of DR.

Inter-visit variability of conjunctival microvascular hemodynamic measurements in healthy and diabetic retinopathy subjects.

Conjunctival microcirculation imaging provides a non-invasive means for detecting hemodynamic alterations due to systemic and ocular diseases. However, reliable longitudinal monitoring of hemodynamic changes due to disease progression requires establishment of measurement variability over time. The purpose of the current study was to determine inter-visit variability of conjunctival microvascular hemodynamic measurements in non-diabetic control (NC, N = 7) and diabetic retinopathy (DR, N = 10) subjects. Conjunctival microvascular imaging was performed during 2 visits, which were 17 ±â€¯12 weeks apart. Images were analyzed to determine vessel diameter (D), axial blood velocity (V), blood flow (Q), wall shear rate (WSR) and wall shear stress (WSS). The inter-visit variability was determined based on mean inter-visit differences. In NC, inter-visit variability of D, V, Q, WSR and WSS were 0.2 ±â€¯0.5 µm, -0.01 ±â€¯0.16 mm/s, -8 ±â€¯46 pl/s, -3 ±â€¯46 s-1 and -0.01 ±â€¯0.10 dyne/cm2, respectively. Inter-visit variability of D, V, Q, WSR and WSS were beyond the normal 95% confidence limits in 60%, 20%, 40%, 20% and 20% of DR subjects, respectively. The variability of hemodynamic measurements over time was established in non-diabetic subjects, suggestive of the potential of the method for detecting longitudinal changes due to progression of DR.

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.

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.

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.

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.

Effects of optical blur reduction on equivalent intrinsic blur.

PURPOSE: To determine the effect of optical blur reduction on equivalent intrinsic blur, an estimate of the blur within the visual system, by comparing optical and equivalent intrinsic blur before and after adaptive optics (AO) correction of wavefront error. METHODS: Twelve visually normal subjects (mean [±SD] age, 31 [±12] years) participated in this study. Equivalent intrinsic blur (σint) was derived using a previously described model. Optical blur (σopt) caused by high-order aberrations was quantified by Shack-Hartmann aberrometry and minimized using AO correction of wavefront error. RESULTS: σopt and σint were significantly reduced and visual acuity was significantly improved after AO correction (p ≤ 0.004). Reductions in σopt and σint were linearly dependent on the values before AO correction (r ≥ 0.94, p ≤ 0.002). The reduction in σint was greater than the reduction in σopt, although it was marginally significant (p = 0.05). σint after AO correlated significantly with σint before AO (r = 0.92, p < 0.001), and the two parameters were related linearly with a slope of 0.46. CONCLUSIONS: Reduction in equivalent intrinsic blur was greater than the reduction in optical blur after AO correction of wavefront error. This finding implies that visual acuity in subjects with high equivalent intrinsic blur can be improved beyond that expected from the reduction in optical blur alone.

Posterior segment toxicity after gemcitabine and docetaxel chemotherapy.

PURPOSE: To report outer retinal disruption and uveal effusion after gemcitabine and docetaxel combination therapy. CASE REPORT: A 78-year-old woman presented with blurry vision after two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity was finger counting and 20/25 in the right and left eyes, respectively. Slit-lamp examination and B-scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B-scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow-up, uveal effusion improved considerably and visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. CONCLUSIONS: Uveal effusion and outer retinal disruption were reported after gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects.

Hemorrhagic Retinopathy after Spondylosis Surgery and Seizure.

PURPOSE: To report bilateral hemorrhagic retinopathy in an adult female subject after lumbar spinal surgery and seizure. CASE REPORT: A 38-year-old woman presented with bilateral blurry vision and spots in the visual field. The patient had lumbar spondylosis surgery that was complicated by a dural tear with persistent cerebrospinal fluid leak. Visual symptoms started immediately after witnessed seizure-like activity. At presentation, visual acuity was 20/100 and 20/25 in the right and left eye, respectively. Dilated fundus examination demonstrated bilateral hemorrhagic retinopathy with subhyaloid, intraretinal, and subretinal involvement. At 4-month follow-up, visual acuity improved to 20/60 and 20/20 in the right and left eye, respectively. Dilated fundus examination and fundus photography showed resolution of retinal hemorrhages in both eyes. CONCLUSIONS: The first case of bilateral hemorrhagic retinopathy after lumbar spondylosis surgery and witnessed seizure in an adult was reported. Ophthalmic examination may be warranted after episodes of seizure in adults.

Correspondence of retinal thinning and vasculopathy in mice with oxygen-induced retinopathy.

The aberrantly vascularized peripheral retina in retinopathy of prematurity (ROP) may be associated with visual field constriction, retinal dysfunction, and abnormalities in retinal thickness which is commonly assessed by spectral domain optical coherence tomography (SDOCT). However, due to the limitation of SDOCT for peripheral retinal imaging, retinal thickness in avascular peripheral retina in ROP has not been evaluated. Oxygen induced retinopathy (OIR) in mice has features of vasculopathy similar to those in human ROP. These features occur in the posterior retina and thereby are accessible by standard imaging methods. The purpose of the current study was to determine the correspondence between abnormalities in retinal thickness and vasculopathy in neonatal OIR mice by simultaneous SDOCT imaging and fluorescein angiography (FA). Newborn mice (N = 19; C57BL/6J strain) were exposed to 77% oxygen from postnatal day 7 (P7) to P12. Age-matched control mice (N = 12) were raised in room air. FA and SDOCT were performed in mice between P17 and P19 to visualize retinal vasculature and measure retinal thickness, respectively. Retinal thickness measurements in vascular regions of interest (ROIs) of control mice, and in hypovascular and avascular ROIs of OIR mice were compared. In control mice, FA showed uniformly dense retinal capillary networks between major retinal vessels and retinal thickness of vascular ROIs was 260 ± 7 µm (N = 12). In OIR mice, FA displayed hypovascular regions with less dense and fewer capillaries and avascular regions devoid of visible capillaries. Retinal thickness measurements of hypovascular and avascular ROIs were 243 ± 21 µm and 209 ± 11 µm (N = 19), respectively. Retinal thickness in hypovascular and avascular ROIs of OIR mice was significantly lower than in vascular ROIs of control mice (p ≤ 0.01). Likewise, retinal thickness in avascular ROIs was significantly lower than in hypovascular ROIs (p < 0.001). Retinal thinning in hypovascular and avascular regions may be due to arrested retinal development and/or ischemia induced apoptosis.

Neural constraints on visual acuity in proliferative diabetic retinopathy.

PURPOSE: Visual acuity (VA) in normally sighted individuals is highly correlated with equivalent intrinsic blur, a measure of the amount of blur within the visual system that is generated by optical and neural sources. This study assessed the extent to which VA, equivalent intrinsic blur, optical blur, and neural blur are abnormal in subjects with proliferative diabetic retinopathy (PDR) and characterized the relationships among these parameters. METHODS: Best-corrected VA of 10 subjects with PDR (ages 25 to 68) and 10 normally sighted individuals (ages 46 to 63) was measured for tumbling E optotypes. The Es were either unblurred or blurred through convolution with Gaussian functions of different widths. Values of equivalent intrinsic blur (σ(int)) and unblurred VA (MAR0) were derived using a standard model. Optical blur (σ(opt)), a measure of blur generated by higher-order aberrations, was quantified using Shack-Hartmann aberrometry. An index of neural blur (η) was defined as 1--σ(opt)/σ(int), which represents the remaining blur once the contributions of σ(opt) to σ(int) have been accounted for. RESULTS: Log MAR0 and log σ(int) were correlated significantly (r = 0.98, p < 0.05) for the PDR subjects and the values of these parameters ranged from normal to more than a factor of 2 above the upper limit of normal. In comparison, log MAR measured for the most blurred E was elevated by a relatively small amount for all PDR subjects and was not correlated significantly with log σ(int) (r = 0.40, p = 0.25). MAR0, σ(int), and η differed significantly between the PDR subjects and the controls (all p < 0.05) but σ(opt) did not (p = 0.50). CONCLUSIONS: Subjects with PDR and VA loss had higher than normal equivalent intrinsic blur that resulted primarily from neural blur elevations, suggesting that neural blur is an important factor that limits VA in these patients.

Wavefront error correction with adaptive optics in diabetic retinopathy.

PURPOSE: To determine the effects of diabetic retinopathy (DR), increased foveal thickness (FT), and adaptive optics (AO) on wavefront aberrations and Shack-Hartmann (SH) image quality. METHODS: Shack-Hartmann aberrometry and wavefront error correction were performed with a bench-top AO retinal imaging system in 10 healthy control and 19 DR subjects. Spectral domain optical coherence tomography was performed and central FT was measured. Based on the FT data in the control group, subjects in the DR group were categorized into two subgroups: those with normal FT and those with increased FT. Shack-Hartmann image quality was assessed based on spot areas, and high-order (HO) root mean square (RMS) and total RMS were calculated. RESULTS: There was a significant effect of DR on HO and total RMS (p = 0.01), and RMS decreased significantly after AO correction (p < 0.001). Shack-Hartmann spot area was significantly affected by DR (p < 0.001), but it did not change after AO correction (p = 0.6). High-order RMS, total RMS, and SH spot area were higher in DR subjects both before and after AO correction. In DR subgroups, HO and total RMS decreased significantly after AO correction (p < 0.001), whereas the effect of increased FT on HO and total RMS was not significant (p ≥ 0.7). There were no significant effects of increased FT and AO on SH spot area (p = 0.9). CONCLUSIONS: Diabetic retinopathy subjects had higher wavefront aberrations and less compact SH spots, likely attributable to pathological changes in the ocular optics. Wavefront aberrations were significantly reduced by AO, although AO performance was suboptimal in DR subjects as compared with control subjects.

Inner retinal oxygen delivery and metabolism in progressive stages of diabetic retinopathy.

Previous studies have reported increased retinal venous oxygen saturation and decreased retinal blood flow and oxygen metabolism in non-proliferative diabetic retinopathy (NPDR). The current study aimed to determine alterations in both inner retinal oxygen delivery (DO2) and metabolism (MO2) in proliferative DR (PDR) as well as at stages of NPDR. A total of 123 subjects participated in the study and were categorized into five groups: non-diabetic control (N = 32), diabetic with no diabetic retinopathy (NDR, N = 34), mild NPDR (N = 31), moderate to severe NPDR (N = 17), or PDR (N = 9). Multi-modal imaging was performed to measure oxygen saturation and blood flow, which were used for derivation of DO2 and MO2. There were significant associations of groups with DO2 and MO2. DO2 was lower in PDR and not significantly different in NDR and NPDR stages as compared to the non-diabetic control group. MO2 was decreased in PDR and moderate to severe NPDR as compared to the control group, and not significantly reduced in NDR and mild NPDR. The findings demonstrate reductions in both DO2 and MO2 in PDR and MO2 in moderate to severe NPDR, suggesting their potential as biomarkers for monitoring progression and treatment of DR.

Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease.

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.