Increased retinal blood flow velocity in patients with early diabetes mellitus.

PURPOSE: To compare retinal blood flow velocity in small vessels of patients with early diabetes mellitus (DM), without any morphologic changes related to diabetic retinopathy, with that in a control group. METHODS: The authors used the retinal function imager to measure blood flow velocities, from many small vessels, simultaneously. Twenty-three eyes of 14 patients with early DM and 51 eyes of 31 healthy subjects were enrolled. Differences between the patients and the control group were assessed by mixed linear models. RESULTS: Venous average velocity significantly increased in the DM group (3.8 ± 1.2 vs. 2.9 ± 0.5 mm/second, P < 0.0001) than in the healthy subjects. Arterial velocity of DM patients was also significantly higher (4.7 ± 1.7 vs. 4.1 ± 0.9 mm/second, P = 0.03). There was no statistically significant difference between groups in age, gender, heart rate, and systolic blood pressure. The diastolic blood pressure in the DM patients was lower than that in the healthy group (P = 0.03). CONCLUSION: There was an increase in arterial and venous retinal blood flow velocities of patients with early DM with no diabetic retinopathy. These findings support the notion that abnormalities in vessel function exist in diabetic eyes before the development of structural changes. This noninvasive approach facilitated the assessment of early hemodynamic abnormalities and may assist in screening and monitoring.

Reduced retinal blood flow velocity in diabetic retinopathy.

PURPOSE: The purpose of this study was to compare the retinal blood flow velocities of patients with diabetes and healthy control subjects. We used a novel device offering a noninvasive diagnostic of retinal function. METHODS: Flow velocities in retinal arterioles and venules were quantitatively analyzed by retinal function imager scanning in 58 eyes of 42 patients with nonproliferative diabetic retinopathy and 51 eyes of 32 normal subjects. Group differences were assessed by the mixed-model effect. RESULTS: Average velocity in arterial compartments (in mm/s) was 3.74 +/- 1.09 for the diabetic group and 4.19 +/- 0.99 for the control subjects. The average velocity of all segments, taking associated heart rate and individual segment widths into account, was 17% slower in the diabetic group (P < 0.0001). In both groups, average venous compartment velocity was lower than the arterial velocity (2.61 +/- 0.65 for the diabetic group; 3.03 +/- 0.59 for the control subjects). Individual vein velocities, taking heart rate and segment widths into account, was 17% slower, on average, in the diabetic group (P < 0.0001). CONCLUSION: Our measurement showed significantly decreased flow velocities in the retinal arterioles and venules of patients with diabetes compared with healthy control subjects, supporting the view of abnormal vessel function in eyes with nonproliferative diabetic retinopathy.

Special report: Noninvasive multi-parameter functional optical imaging of the eye.

Advancement in the treatment of blindness depends on the development of new technologies that enable early detection, follow-up, and treatment of disease. The authors describe direct, noninvasive imaging of four parameters: blood flow, blood oximetry, metabolic state, and hidden vasculature, particularly capillaries. These are functional parameters of the retina known to be degraded by retinal disease. The new Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel) can image all four parameters as intrinsic reflectance intensity differences over the retina's surface. During the past 2 decades, imaging of small optical signals has been a powerful tool for high-resolution functional mapping in the neocortex. In this article, this technology is applied to the retina and demonstrates a general tool for noninvasively probing retinal function in many modalities. Imaging functional changes before anatomic consequences arise holds promise as a powerful tool for early diagnosis and treatment of retinal disease.

High-resolution functional optical imaging: from the neocortex to the eye.

Much work remains to be done to establish the clinical usefulness of the RFI for early diagnosis and treatment guidance. The discoveries obtained by functional optical imaging of the neocortex in the last 15 years and the recent RFI studies of the eyes of normal subjects and patients with diabetic retinopathy, glaucoma, and age-related macular degeneration suggest that functional optical imaging of the retina is likely to become a multi-modality powerful clinical tool.

Retinal blood flow velocity in patients with age-related macular degeneration.

PURPOSE/AIM OF THE STUDY: To study changes in retinal blood flow velocity in patients with early and neovascular age-related macular degeneration (AMD). We used the Retinal Function Imager (RFI, Optical Imaging Ltd., Rehovot, Israel), a noninvasive diagnostic approach for measuring blood flow velocity. MATERIALS AND METHODS: Sixty eyes of 43 AMD patients and 53 eyes of 35 healthy individuals over the age of 50 were recruited for this study. All patients were scanned by the RFI with analysis of blood flow velocity of secondary and tertiary branches of arteries and veins. Differences among groups were assessed by mixed linear models. RESULTS: The average velocity in AMD patients was significantly lower compared to controls in arteries (3.6 ± 1.4 versus 4.3 ± 1.0 mm/sec, p = 0.009) but not in veins (2.6 ± 0.9 versus 3.1 ± 0.6 mm/sec, p = 0.08). When comparing the velocity between low- and high-grade AMD eyes, venous velocity was slower in the high grade AMD eyes only in the "narrow" group of vessels. CONCLUSIONS: Decreased blood flow velocity in retinal arteries in patients with AMD was found. Despite the fact that AMD is essentially a choroidal disease, retinal vessels show a functional abnormality, which may suggest that the vascular abnormality in this disease is more generalized.

The correlation between retinal blood flow velocity measured by the retinal function imager and various physiological parameters.

BACKGROUND AND OBJECTIVE: The retinal function imager (RFI) (Optical Imaging Ltd., Rehovot, Israel) measures retinal blood flow velocity non-invasively. The authors studied the reproducibility of these measurements and assessed the effect of physiological components on them. PATIENTS AND METHODS: Sixty-seven individuals with no retinal pathology were recruited. Velocity reproducibility was verified by comparing repeated RFI measurements. The correlation of the velocity with physiological parameters was assessed by mixed linear and Gaussian models. RESULTS: The average velocity was 4.2 ± 0.9 mm/sec arterial and 3.3 ± 0.8 mm/sec venous. Variability was 7.5% ± 3.7% and interclass correlation coefficient was r = 0.744. Venous velocity decreased after 40 years of age (0.32 mm/sec per decade, P < .01). Arterial velocity increased as mean arterial pressure increased (0.25 mm/sec per 10 mm Hg, P < .01). There was also a positive association between velocities and heart rate (arteries: 0.21 mm/sec per 10 bpm, P < .05; veins: 0.22 mm/sec per 10 bpm, P < .01). CONCLUSION: The RFI provides a reproducible, non-invasive technique to assess retinal velocities.

The effect of intravitreal bevacizumab (Avastin) injection on retinal blood flow velocity in patients with choroidal neovascularization.

PURPOSE: To study the short-term effects of intravitreal bevacizumab (Avastin) on retinal blood flow velocity and compare them to clinical outcomes assessed by optical coherence tomography (OCT) and tests of visual acuity. METHODS: The Retinal Function Imager (RFI) was used noninvasively and quantitatively to measure retinal blood flow velocity. Eight patients receiving intravitreal injection of Avastin for choroidal neovascularization (CNV) were included in this study. All were imaged by the RFI preinjection and 1 and 7 days postinjection. Visual acuity (VA) and OCT were recorded preinjection and 1 month postinjection. Comparisons were performed using paired Student t test and correlation using Spearman rank test. RESULTS: A good correlation was found between the 1-month change in VA and OCT measurements and the short-term change induced in blood flow velocity. Arterial and venous velocity changes 1 day after the injection correlated with the VA change (p<0.05). The 1-day arterial velocity changes correlated with total macular volume (p=0.02) and venous velocity changes correlated to central macular thickness (p = 0.04). CONCLUSIONS: The RFI provides a noninvasive technique to assess early hemodynamic responses to intravitreal injection of Avastin. These early changes may prove important for better understanding of the mechanism underlying this treatment and serve as a quantitative marker for treatment optimization.

High-resolution wide-field imaging of perfused capillaries without the use of contrast agent.

PURPOSE: Assessment of capillary abnormalities facilitates early diagnosis, treatment, and follow-up of common retinal pathologies. Injected contrast agents like fluorescein are widely used to image retinal capillaries, but this highly effective procedure has a few disadvantages, such as untoward side effects, inconvenience of injection, and brevity of the time window for clear visualization. The retinal function imager (RFI) is a tool for monitoring retinal functions, such as blood velocity and oximetry, based on intrinsic signals. Here we describe the clinical use of hemoglobin in red blood cells (RBCs) as an intrinsic motion-contrast agent in the generation of detailed noninvasive capillary-perfusion maps (nCPMs). PATIENTS AND METHODS: Multiple series of nCPM images were acquired from 130 patients with diabetic retinopathy, vein occlusion, central serous retinopathy, age-related macular degeneration, or metabolic syndrome, as well as from 37 healthy subjects. After registration, pixel value distribution parameters were analyzed to locate RBC motion. RESULTS: The RFI yielded nCPMs demonstrating microvascular morphology including capillaries in exquisite detail. Maps from the same subject were highly reproducible in repeated measurements, in as much detail and often better than that revealed by the very best fluorescein angiography. In patients, neovascularization and capillary nonperfusion areas were clearly observed. Foveal avascular zones (FAZ) were sharply delineated and were larger in patients with diabetic retinopathy than in controls (FAZ diameter: 641.5 ± 82.3 versus 463.7 ± 105 µm; P < 0.001). Also visible were abnormal vascular patterns, such as shunts and vascular loops. CONCLUSION: Optical imaging of retinal capillaries in human patients based on motion contrast is noninvasive, comfortable, safe, and can be repeated as often as required for early diagnosis, treatment guidance, and follow up of retinal disease progression.

Functional imaging using the retinal function imager: direct imaging of blood velocity, achieving fluorescein angiography-like images without any contrast agent, qualitative oximetry, and functional metabolic signals.

The Retinal Function Imager (RFI; Optical Imaging, Rehovot, Israel) is a unique, noninvasive multiparameter functional imaging instrument that directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, and metabolic responses to photic activation. In addition, it allows capillary perfusion mapping without any contrast agent. These parameters of retinal function are degraded by retinal abnormalities. This review delineates the development of these parameters and demonstrates their clinical applicability for noninvasive detection of retinal function in several modalities. The results suggest multiple clinical applications for early diagnosis of retinal diseases and possible critical guidance of their treatment.