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Purpose : To assess the agreement between Line 3-5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement. Methods : 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3-5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed. Results : There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p < .001; arterial: ICCs = 0.84, p < .001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p < .001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 μm - 1799 μm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p < .001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 μm/μm ( p < .001) and 0.007 μm/μm ( p = .02), respectively. Conclusion : Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used.

We investigated the characteristics of microvessel tortuosity in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) and their associations with visual outcomes using optical coherence tomography angiography (OCTA). Thirty-four BRVO and 21 CRVO patients and 31 healthy subjects were included. From OCTA, the branch number (BN), mean branch length (BL), mean Euclidean length (EL), vessel density (VD) and vessel tortuosity (VT) were quantified. In BRVO eyes, compared with that in the controls, the affected area of the deep capillary plexus (DCP) showed a decreased BN and VD, an increased BL, and unchanged VT. The nonaffected area of the DCP showed decreases in BN, VD and VT. The affected area of the superficial capillary plexus (SCP) showed higher VT. In CRVO eyes, the DCP showed a lower BN, VD and VT, while the SCP showed a lower BN and greater BL and EL. Improved visual acuity (VA) after 1 year in BRVO eyes was associated with decreases in BN, BL, VD and VT in the affected area in the DCP and lower VT in the nonaffected area of the SCP; in CRVO eyes, improved VA was associated with a higher BL and EL in the DCP. VT, BL, and EL may be new microvascular markers associated with changes in VA in BRVO and CRVO.

Purpose: To introduce a simple method for differentiating retinal veins from arteries on optical coherence tomography angiography (OCTA)., Design: Cross-sectional pilot study., Methods: Four default en face slabs including color depth encoded, grayscale full-thickness retina, superficial plexus, and deep capillary plexus (DCP) from nine 3×3-mm and nine 6×6-mm OCTA scans were exported and aligned. Nine ophthalmologists with minimum OCTA experience from 2 eye institutions were instructed to classify labeled vessels as arteries or veins in 3 stages. Classification was performed based on graders' own assessment at stage 1. Graders were taught that a capillary-free zone was an anatomic feature of arteries at stage 2 and were trained to identify veins originating from vortices within the DCP at stage 3. Grading accuracy was analyzed and correlated with grading time and graders' years in practice., Results: Overall grading accuracy in stages 1, 2, and 3 was (50.4% ± 17.0%), (75.4% ± 6.0%), and (94.7% ± 2.6%), respectively. Grading accuracy for 3×3-mm scans in stages 1, 2, and 3 was (49.9% ± 16.3%), (79.2% ± 9.6%), and (96.9% ± 3.1%), respectively. Accuracy for 6×6-mm scans in stages 1, 2, and 3 was (51.4% ± 20.8%), (72.3% ± 7.9%), and (93.2% ± 3.3%), respectively. Grading performance improved significantly at each stage (all P < .001). No significant correlation was found between accuracy and time spent grading or between accuracy and years in practice (r = -0.164 to 0.617, all P ≥ .077)., Conclusions: We describe a simple method for accurately distinguishing retinal arteries from veins on OCTA, which incorporates the use of vortices in the DCP to identify venous origin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate associations of central retinal arteriolar equivalent (CRAE), a measure of retinal arteriolar width, and central retinal venular equivalents (CRVE), a measure of retinal venular width, with shiftwork in 199 police officers (72.9% men)., Methods: Shiftwork (day, afternoon, night) was assessed using electronic payroll records. Four digital retinal images per officer were taken. Mean diameters of the retinal vasculature were compared across shifts using analysis of variance (ANOVA)/analysis of covariance (ANCOVA)., Results: Among all officers (mean age = 46.6 ± 6.8 years), shiftwork was not significantly associated with CRAE or CRVE. However, among current and former smokers, night-shift officers had a wider mean (±standard error [SE]) CRVE (230.0 ± 4.5 μm) compared with day shift officers (215.1 ± 3.5 μm); adjusted P = 0.014., Conclusions: Night shift schedule in current and former smokers is associated with wider retinal venules. Reasons for this association are not known. Longitudinal studies are warranted.

Purpose: To measure the effect of nonproliferative diabetic retinopathy (NPDR) on retinal branching. To compare vascular branching in healthy and diabetic subjects with established biophysical models., Methods: Vascular bifurcations in arteries and veins were imaged in 17 NPDR and 26 healthy subjects with the Indiana adaptive optics scanning laser ophthalmoscope (AOSLO). Vessel measurements were grouped according to parent vessel diameters into large (≤50 ∼ <100 μm) and small (≤20 ∼ <50 μm) sizes. Vessel diameters and bifurcation angles were measured manually. Vascular diameters were compared with predictions of Murray's law using curve fitting. For analysis of bifurcation angles, two models from Zamir were compared: one based on the power required for blood pumping, the other based on drag force between blood and vascular wall., Results: For normal larger vessels, the exponent relating the parent and daughter branching diameters was significantly less than the value of 3 predicted by Murray's law (arteries: 2.59; veins: 1.95). In NPDR, the best-fit exponent was close to 3 for arteries but close to 2 in healthy subjects in veins, (arteries: 3.09; veins: 2.16). For both small arteries and veins, diabetics' exponent differed from healthy subjects (P < 0.01). Bifurcation angles in the healthy subjects (78° ± with a standard error (SE) of 0.9°) were not much different than in NPDR (79° ± SE 1.3°). The model based on minimizing pumping power predicted the measurements better than the one minimizing the vascular drag and lumen surface area., Conclusions: The relation between parent and daughter branch diameters changes in diabetes, but the branching angles do not.

Ocular vasculature consists of the central retinal and ciliary vascular systems, which are essential to maintaining visual function. Many researchers have attempted to determine their origins and development; however, the detailed, stepwise process of ocular vasculature formation has not been established. In zebrafish, two angioblast clusters, the rostral and midbrain organizing centers, form almost all of the cranial vasculature, including the ocular vasculature, and these are from where the cerebral arterial and venous angioblast clusters, respectively, differentiate. In this study, we first determined the anatomical architecture of the primary ocular vasculature and then followed its path from the two cerebral angioblast clusters using a time-lapse analysis of living Tg(flk1:EGFP)k7 zebrafish embryos, in which the endothelial cells specifically expressed enhanced green fluorescent protein. We succeeded in capturing images of the primary ocular vasculature formation and were able to determine the origin of each ocular vessel. In zebrafish, the hyaloid and ciliary arterial systems first organized independently, and then anastomosed via the inner optic circle on the surface of the lens by the lateral transfer of the optic vein. Finally, the choroidal vascular plexus formed around the eyeball to complete the primary ocular vasculature formation. To our knowledge, this study is the first to report successful capture of circular integration of the optic artery and vein, lateral transfer of the optic vein to integrate the hyaloidal and superficial ocular vasculatures, and formation of the choroidal vascular plexus. Furthermore, this new morphological information enables us to assess the entire process of the primary ocular vasculature formation, which will be useful for its precise understanding.

The constant inflow and variable outflow (CIVO) theory correctly predicts that spontaneous pulsation of the retinal veins will be visible close to the point where the vein exits the eye at the lamina cribrosa but will decrease rapidly in amplitude and become too small to see only a short distance upstream. However, the phase of vein oscillation relative to the oscillation of the intraocular pressure (IOP) predicted by CIVO has been unclear and controversial. We show that the CIVO model is indeterminate in predicting such phase relations. We propose a simple extension of the CIVO model that retains its basic equations but applies them to a larger domain that includes not only the intraocular (pre-laminar) portion of the vein but also the retrobulbar (post-laminar) portion of the vein behind the eye. We show that this extended CIVO model makes definite predictions about the phase of vein oscillation relative to the oscillation of IOP. This phase relationship is determined by the relative amplitude and phase of pulsations of the IOP and of the cerebrospinal fluid pressure (CSFP). If IOP and CSFP oscillate in phase, then the pre-laminar vein oscillates in phase with IOP when the amplitude of CSFP exceeds the amplitude of IOP but oscillates in counter phase with IOP when the amplitude of IOP exceeds that of CSFP. These relationships are modified when there is a phase difference between the oscillations of IOP and CSFP. When CSFP leads IOP, the phase of vein oscillation is advanced if the amplitude of CSFP exceeds that of IOP and is delayed if the amplitude of IOP exceeds that of CSFP. The result in each case is that maximum vein size occurs during the rising phase of IOP (ocular systole). We conclude that the driving force of vein oscillation is the difference between the oscillations of IOP and CSFP. The phase of this difference determines the phase relationships above. We show that additional delays in the phase of venous pulsation relative to that of IOP are induced by constriction of the vein within the lamina cribrosa and by recording the vein pulsations upstream from the lamina cribrosa. The amplitude of vein oscillation is proportional to the amplitude of the driving force and to the venous capacitance. Loss of spontaneous retinal vein pulsation with increase in mean CSFP is determined primarily by reduced venous capacitance. Increased amplitude of pulsation may occur when IOP is increased. It is the result of increased venous capacitance and possibly increased driving force of the pulsation. However, in chronic glaucoma the increase in capacitance may be counteracted by venous outflow obstruction, and the increase in driving force may be counteracted by reduced ocular blood flow. As a result retinal vein oscillation may be reduced in amplitude., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Abnormalities of blood vessel anatomy, morphology, and ratio can serve as important diagnostic markers for retinal diseases such as AMD or diabetic retinopathy. Large cohort studies demand automated and quantitative image analysis of vascular abnormalities. Therefore, we developed an analytical software tool to enable automated standardized classification of blood vessels supporting clinical reading., Methods: A dataset of 61 images was collected from a total of 33 women and 8 men with a median age of 38 years. The pupils were not dilated, and images were taken after dark adaption. In contrast to current methods in which classification is based on vessel profile intensity averages, and similar to human vision, local color contrast was chosen as a discriminator to allow artery vein discrimination and arterial-venous ratio (AVR) calculation without vessel tracking., Results: With 83% ± 1 standard error of the mean for our dataset, we achieved best classification for weighted lightness information from a combination of the red, green, and blue channels. Tested on an independent dataset, our method reached 89% correct classification, which, when benchmarked against conventional ophthalmologic classification, shows significantly improved classification scores., Conclusions: Our study demonstrates that vessel classification based on local color contrast can cope with inter- or intraimage lightness variability and allows consistent AVR calculation. We offer an open-source implementation of this method upon request, which can be integrated into existing tool sets and applied to general diagnostic exams.

Background: Summarised retinal vessel diameters are linked to systemic vascular pathology. Monochromatic images provide best contrast to measure vessel calibres. However, when obtaining images with a dual wavelength oximeter the red-free image can be extracted as the green channel information only which in turn will reduce the number of photographs taken at a given time. This will reduce patient exposure to the camera flash and could provide sufficient quality images to reliably measure vessel calibres., Methods: We obtained retinal images of one eye of 45 healthy participants. Central retinal arteriolar and central retinal venular equivalents (CRAE and CRVE, respectively) were measured using semi-automated software from two monochromatic images: one taken with a red-free filter and one extracted from the green channel of a dual wavelength oximetry image., Results: Participants were aged between 21 and 62 years, all were normotensive (SBP: 115 (12) mmHg; DBP: 72 (10) mmHg) and had normal intra-ocular pressures (12 (3) mmHg). Bland-Altman analysis revealed good agreement of CRAE and CRVE as obtained from both images (mean bias CRAE = 0.88; CRVE = 2.82)., Conclusions: Summarised retinal vessel calibre measurements obtained from oximetry images are in good agreement to those obtained using red-free photographs.

We propose a novel, graph-theoretic framework for distinguishing arteries from veins in a fundus image. We make use of the underlying vessel topology to better classify small and midsized vessels. We extend our previously proposed tree topology estimation framework by incorporating expert, domain-specific features to construct a simple, yet powerful global likelihood model. We efficiently maximize this model by iteratively exploring the space of possible solutions consistent with the projected vessels. We tested our method on four retinal datasets and achieved classification accuracies of 91.0%, 93.5%, 91.7%, and 90.9%, outperforming existing methods. Our results show the effectiveness of our approach, which is capable of analyzing the entire vasculature, including peripheral vessels, in wide field-of-view fundus photographs. This topology-based method is a potentially important tool for diagnosing diseases with retinal vascular manifestation.

Purpose: To describe the macular deep capillary plexus (DCP) in normal eyes using optical coherence tomography angiography., Methods: Retrospective study including 41 consecutive normal eyes imaged using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc). Default autosegmentation of the superficial capillary plexus (SCP) and DCP, and manual adjustments of "deep settings" were used to analyze the organization of the normal macular microvascularization and to investigate in vivo the connection between these capillary networks., Results: Mean age was 31 years (range, 22-55 years). The SCP and DCP had 2 different organizations, but the plexus autosegmentation was imperfect: In 68% of cases, the image of the SCP variably superimposed on the DCP, interfering with its analysis. The SCP was composed on average of 7 pairs of arterioles and venules obvious on each 3-mm × 3-mm optical coherence tomography angiography scanning area. The DCP was composed of a capillary vortex arrangement, whose centers were aligned along the course of the macular superficial venules., Conclusion: The SCP and DCP had two different topographic organizations. The pattern of the capillary units converging into capillary vortexes highly suggests that they drain into the superficial venules. The different structural properties of the SCP and DCP could explain the differences in flow resistance and perfusion.

Purpose: To compare the Parr-Hubbard and Knudtson formulas to calculate retinal vessel calibers and to examine the effect of omitting vessels on the overall result., Methods: We calculated the central retinal arterial equivalent (CRAE) and central retinal venular equivalent (CRVE) according to the formulas described by Parr-Hubbard and Knudtson including the six largest retinal arterioles and venules crossing through a concentric ring segment (measurement zone) around the optic nerve head. Once calculated, we removed one arbitrarily selected artery and one arbitrarily selected vein and recalculated all outcome parameters again for (1) omitting one artery only, (2) omitting one vein only, and (3) omitting one artery and one vein. All parameters were compared against each other., Results: Both methods showed good correlation (r 2for CRAE = 0.58; r2 for CRVE = 0.84), but absolute values for CRAE and CRVE were significantly different from each other when comparing both methods (p < 0.000001): CRAE had higher values for the Parr-Hubbard (165 [± 16] μm) method compared with the Knudtson method (148 [± 15] μm). In addition, CRAE and CRVE values dropped for both methods when omitting one arbitrarily selected vessel each (all p < 0.000001). Arteriovenous ratio (AVR) calculations showed a similar change for both methods when omitting one vessel each: AVR decreased when omitting one arteriole whereas it increased when omitting one venule. No change, however, was observed for AVR calculated with six or five vessel pairs each., Conclusions: Although the absolute value for CRAE and CRVE is changing significantly depending on the number of vessels included, AVR appears to be comparable as long as the same number of arterioles and venules is included.

Purpose: The purpose of this study was to investigate the effects of aging on anteroposterior tortuosity of the retinal vein at the arteriovenous (AV) crossing in healthy subjects., Methods: We examined 48 eyes of 24 healthy older Japanese subjects (>60 years), and, as controls, 42 eyes of 21 healthy younger Japanese subjects (<30 years). Retinal vein images at the AV crossing were obtained by optical coherence tomography. The depth of the vein was measured vertically from the outer border of the retinal pigment epithelium to the outer vein wall. We defined "m" as the deepest point of the vein at the AV crossing and "M" as the shallowest point. To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio m/M., Results: Mean m, M, and m/M in older subjects were 76.5 ± 13.1 µm, 142.7 ± 21.2 µm, and 0.52 ± 0.09, respectively. In younger control subjects, the values were 64.1 ± 12.6 µm, 139.9 ± 22.4 µm, and 0.46 ± 0.06. The values of "M" were not significantly different between groups, whereas both "m/M" and "m" were significantly (p = 0.021) lower in the older subjects than in the younger subjects., Conclusion: Anteroposterior tortuosity of the retinal vein was evaluated based on the maximum and minimum retinal vein depth measurements at the AV crossing using optical coherence tomography. Anteroposterior tortuosity of the retinal vein at the AV crossing is increased with age.

Objective: To examine the longitudinal relationship between changes in childhood body mass index (BMI) and retinal vascular caliber., Study Design: A prospective study of 421 healthy children aged 7-9 years in 2001 who returned for follow-up in 2006. At both visits, retinal photographs and anthropometric measurements were taken following standardized protocols. Retinal arteriolar and venular calibers were measured using a computer-based program and summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)., Results: At follow-up, mean weight, height, and BMI increased significantly (P < .001). Mean CRVE increased by 3.4 μm (P < .001) but mean CRAE did not alter significantly (P = .340). On multivariate analysis, greater BMI was cross-sectionally associated with narrower CRAE (P < .01) and wider CRVE (P < .01). On longitudinal analysis, increasing BMI was associated with increasing CRVE (P = .04) over the 5-year period. Baseline BMI was associated with increased venular caliber and decreased arteriolar caliber at follow-up, and vice versa (P < .05)., Conclusions: Increasing BMI is associated with increasing retinal venular caliber over time in children, and baseline retinal vascular caliber changes increase the risk of higher BMI at follow-up. As both widened retinal venular caliber and greater BMI are associated with risk of cardiovascular events in adults, progressive retinal venular widening could be a manifestation of an adverse microvascular effect of obesity early in life., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To analyze device-dependent variability of two non-mydriatic fundus cameras to obtain arterio-venous ratio (AVR), central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE) in static vessel analysis (SVA)., Methods: We examined 53 participants (29 men, 24 women; median age 46 years) of the Study of Health in Pomerania (SHIP). We took 45° optic-disc-centered fundus images of the right eye with two different non-mydriatic fundus cameras. The first photograph was obtained from the TRC-NW 200, the second from the OCT 2000 (both Topcon Corporation, Tokyo, Japan). One experienced grader graded image quality from 1 "ideal quality" to 5 "not analyzable" and determined AVR, CRAE, and CRVE with the software Vesselmap3 (Imedos, Jena, Germany)., Results: Average image quality was 1.8 for the TRC-NW 200 and 1.6 for the OCT 2000. AVR could not be determined in 5 images of the TRC-NW 200 due to low image quality, while six images of the OCT 2000 were not analyzable. The difference between AVR taken from two different non-mydriatic cameras was 0.01 ± 0.03 in Bland-Altman plots. The difference between CRAE was 0.17 ± 10.15 and between CRVE was -2.32 ± 11.76., Conclusions: The two different non-mydriatic cameras showed good agreement with respect to image quality. When using the same reading software, AVR, CRAE, and CRVE agreed well. Thus, funduscopy and SVA seem to be robust against inter-device variability. As a result, device dependency can remain unconsidered in follow-up examinations with different technical equipment. However, variability might impact more with devices from different manufacturers.

This study was conducted to demonstrate a new scan method for retinal vessel structure measurement in a specific region of fundus (zone B) using spectral-domain optical coherence tomography (SD-OCT), and to assess its reliability. One temporal superior retinal vessel pair passing through a concentric ring (zone B), which was defined between half and one disc distance from the optic disc border, was chosen for the measurement using a volume scan in SD-OCT. On the SD-OCT image, retinal arteriolar outer diameter (RAOD), retinal arteriolar lumen diameter (RALD), retinal venular outer diameter (RVOD) and retinal venular lumen diameter (RVLD) were measured. Retinal vessel diameters on color fundus photographs were also analyzed. Fifty-five healthy individuals were recruited to evaluate intraobserver and interobserver reproducibility between the two examiners. The intraobserver intraclass correlation coefficient (ICC) ranged from 0.972 to 0.981, and the interobserver ICC ranged from 0.968 to 0.980. In the Bland-Altman plot, the 95% limits of interobserver agreement for the RAOD, RALD, RVOD and RVLD were -5.60 to 4.84μm, -5.78 to 5.05μm, -7.52 to 5.62μm and -7.10 to 5.63μm, respectively. The retinal arteriolar and venular lumen diameters on the SD-OCT image were close to the mean arteriolar and venular diameters obtained from the color fundus photographs. Volume scan method produced better images of retinal vessels showing the fine structures of the vessel wall, and provided reliable retinal vessel structure measurement in zone B with good repeatability and reproducibility., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To study the three-dimensional morphologic features of retinal arteriovenous crossings with optical coherence tomography (OCT) and elucidate the vascular changes associated with crossing phenomena as seen on fundus photographs., Methods: We examined 150 consecutive eyes with no ocular disease. In each eye, fundus photographs were taken, and one randomly selected arteriovenous crossing was examined by OCT. The OCT analysis was performed by using sequential thin sections along and perpendicular to the retinal vessels., Results: The OCT analysis of these arteriovenous crossings showed that the veins abruptly changed their directions to pass the artery and frequently displayed focal luminal narrowing with no compression or flattening. The OCT measurements revealed that the veins narrowed by 21.0% ± 12.9% at the crossings. The degree of narrowing correlated positively with the diameter of the crossing arteries (r = 0.419, P < 0.001). On fundus photographs, crossing phenomena were observed in 103 of the 150 selected crossings. Venous narrowing measured by OCT was more severe in eyes with crossing phenomena on fundus photographs (P < 0.001). Four types of crossing phenomena were observed: concealment, tapering, deflection, and humping. Venous narrowing rates were similar among all four types. Although the subjects with deflection or humping phenomena were more likely to suffer from hypertension, the mean venous narrowing rate at such crossings was similar to that observed with the other crossing phenomena., Conclusions: Arteriovenous crossings exhibited focal narrowing of the venous lumen with no compression or flattening. Increased venous narrowing and larger arteries were observed at crossings with crossing phenomena.

Purpose: Funduscopic assessment of the retinal vessels may be used to assess the health status of microcirculation and as a component in the evaluation of cardiovascular risk factors. Typically, the evaluation is restricted to morphological appreciation without strict quantification. Our purpose was to develop and validate a software tool for semi-automated quantitative analysis of retinal vasculature in nonmydriatic fundus photography., Methods: matlab software was used to develop a semi-automated image recognition and analysis tool for the determination of the arterial-venous (A/V) ratio in the central vessel equivalent on 45° digital fundus photographs. Validity and reproducibility of the results were ascertained using nonmydriatic photographs of 50 eyes from 25 subjects recorded from a 3DOCT device (Topcon Corp.). Two hundred and thirty-three eyes of 121 healthy subjects were evaluated to define normative values., Results: A software tool was developed using image thresholds for vessel recognition and vessel width calculation in a semi-automated three-step procedure: vessel recognition on the photograph and artery/vein designation, width measurement and calculation of central retinal vessel equivalents. Mean vessel recognition rate was 78%, vessel class designation rate 75% and reproducibility between 0.78 and 0.91. Mean A/V ratio was 0.84. Application on a healthy norm cohort showed high congruence with prior published manual methods. Processing time per image was one minute., Conclusions: Quantitative geometrical assessment of the retinal vasculature may be performed in a semi-automated manner using dedicated software tools. Yielding reproducible numerical data within a short time leap, this may contribute additional value to mere morphological estimates in the clinical evaluation of fundus photographs., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To examine the effects of various cardiovascular, ocular, and lifestyle factors on retinal vessel diameters over short periods of time., Methods: Subjects were invited to have photographs of their retina taken at each of three study visits. The same eye was photographed each time. The photographs were digitized and retinal vessel diameters were measured. Measurements from the retinal photographs taken consecutively (at visit 2 and visit 3), and 1, 3, and 4 weeks apart (between visits 1 and 2, 2 and 3, and 1 and 3, respectively) were compared., Results: There were 63 persons who participated in all study visits and had gradable vessel measurements from all five images used in the analysis. Correlations for pairs of study visits were high, and decreased slightly with increasing length of the time interval. For consecutive photographs taken, and 1 week, 3 weeks, and 4 weeks apart, correlations were 0.95, 0.90, 0.91, and 0.86, respectively, for central retinal arteriolar equivalent (CRAE) and 0.95, 0.90, 0.91, and 0.87, respectively, for central retinal venular equivalent (CRVE). We examined the associations of blood pressure levels, smoking habits, time since last eating, exercising, consuming caffeine, and taking anti-hypertensive medication, and image focus with CRAE and CRVE. We found no consistent pattern of association of any of these characteristics with short-term changes in CRAE and CRVE., Conclusion: Retinal vessel diameters are stable over short intervals of time and none of the factors studied were consistently associated with change in the diameters of either vessel type.

Purpose: To describe a method for measuring the diameters of large retinal blood vessels by means of spectral domain optical coherence tomography., Methods: Prospective cohort study of 29 healthy subjects (58 eyes) who underwent a spectral domain optical coherence tomography examination. Two cubes of horizontal scans were placed at the superior and inferior borders of the disk to include the large temporal retinal vessels. Vessels diameters were measured, and an artery-to-vein ratio was calculated at 10 measurement points (480-1440 μm superiorly and inferiorly from the optic disk border)., Results: The mean age of the study subjects was 41.45 ± 15.53 years. Patients had no ocular or systemic pathologies. The mean diameter of the retinal artery was 135.73 ± 15.64 μm and of the vein 151.32 ± 15.22 μm at the measurement point of 480 μm, with a gradual decrease to 123.01 ± 13.43 μm and 137.69 ± 13.84 μm, respectively, at 1440 μm. The artery-to-vein ratio was ≈ 0.9 at all points of measurement., Conclusion: This is a new noninvasive method for retinal blood vessels diameter measurement using the spectral domain optical coherence tomography imaging modality. This method may aid in evaluation of retinal and systemic vascular diseases.

In recent years researchers have found that alternations in arterial or venular tree of the retinal vasculature are associated with several public health problems such as diabetic retinopathy which is also the leading cause of blindness in the world. A prerequisite for automated assessment of subtle changes in arteries and veins, is to accurately separate those vessels from each other. This is a difficult task due to high similarity between arteries and veins in addition to variation of color and non-uniform illumination inter and intra retinal images. In this paper a novel structural and automated method is presented for artery/vein classification of blood vessels in retinal images. The proposed method consists of three main steps. In the first step, several image enhancement techniques are employed to improve the images. Then a specific feature extraction process is applied to separate major arteries from veins. Indeed, vessels are divided to smaller segments and feature extraction and vessel classification are applied to each small vessel segment instead of each vessel point. Finally, a post processing step is added to improve the results obtained from the previous step using structural characteristics of the retinal vascular network. In the last stage, vessel features at intersection and bifurcation points are processed for detection of arterial and venular sub trees. Ultimately vessel labels are revised by publishing the dominant label through each identified connected tree of arteries or veins. Evaluation of the proposed approach against two different datasets of retinal images including DRIVE database demonstrates the good performance and robustness of the method. The proposed method may be used for determination of arteriolar to venular diameter ratio in retinal images. Also the proposed method potentially allows for further investigation of labels of thinner arteries and veins which might be found by tracing them back to the major vessels., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Recent research suggests that retinal vessel caliber (or cross-sectional width) measured from retinal photographs is an important feature for predicting cardiovascular diseases (CVDs). One of the most utilized measures is to quantify retinal arteriolar and venular caliber as the Central Retinal Artery Equivalent (CRAE) and Central Retinal Vein Equivalent (CRVE). However, current computer tools utilize manual or semi-automatic grading methods to estimate CRAE and CRVE. These methods involve a significant amount of grader's time and can add a significant level of inaccuracy due to repetitive nature of grading and intragrader distances. An automatic and time efficient grading of the vessel caliber with highly repeatable measurement is essential, but is technically challenging due to a substantial variation of the retinal blood vessels' properties. In this paper, we propose a new technique to measure the retinal vessel caliber, which is an "edge-based" vessel tracking method. We measured CRAE and CRVE from each of the vessel types. We achieve very high accuracy (average 96.23%) for each of the cross-sectional width measurement compared to manually graded width. For overall vessel caliber measurement accuracy of CRAE and CRVE, we compared the results with an existing semi-automatic method which showed high correlation of 0.85 and 0.92, respectively. The intra-grader reproducibility of our method was high, with the correlation coefficient of 0.881 for CRAE and 0.875 for CRVE., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aim: To identify the relationship of retinal arteries in a population with systemic arterial hypertension., Methods: High resolution, dilated, digitised, fundus photographs of consecutive patients with a history of hypertension requiring pharmacologic therapy seen on the Wills Eye Hospital Retina Service were analysed. Included were photographs of the temporal retinal vascular arcades in which media clarity permitted good visualisation of third-order retinal vascular bifurcations. Each first- and second-order arteriovenous (AV) crossing was then examined to identify anatomic patterns at the sites where veins and arteries crossed. Eyes in patients without a history of hypertension were used as controls., Results: Among the 71 patients (134 eyes), there were 430 first-order and second-order AV crossings, in which AV nicking was present at 126 sites. A retinal artery was located anterior to the retinal vein in 122 of the 126 sites (96.8%) at which AV nicking was noted, while nicking associated with the vein located anteriorly to the artery occurred in only 4 of 126 (3.2%) of AV crossings (p<0.001). An anatomical pattern of venous arching, or cascading of a retinal vein over a retinal artery, was noted predominantly when the vein was positioned anterior to the artery in both subjects and controls. Among the 43 venous arching sites in the study group, 41 (95.3%) demonstrated the retinal vein anterior to retinal artery (p<0.001)., Conclusions: In patients with systemic arterial hypertension and hypertensive retinopathy, AV nicking of the retinal vein at the site of AV crossing is seen predominantly when the retinal artery lies anterior to the vein, but generally not when the vein lies anterior to the artery. The clinician should realise that when a retinal vein lies anterior to a retinal artery, the absence of AV nicking does not rule out more severe, chronic, retinopathic changes than observed with retinal arterial straightening only.

Objective: To investigate the association of urinary albumin-to-creatinine ratio (UACR) and the diameter of retinal vessel in population with essential hypertension in Fujian coastal area., Methods: Central retinal artery and vein equivalents (CRAE and CRVE) were measured from the avoiding mydriatic digitized photographs and semi-automatic fundus analysis software, as well as albumin and urine creatinine., Results: There were significant differences in CRAE levels among the normal control group, normoalbuminuria with essential hypertension group and microalbuminuria with essential hypertension group [(135.68 ± 10.10) µm, (129.79 ± 10.48) µm, (125.29 ± 11.17) µm, all P values < 0.01]. The CRAE levels were significantly negative correlated with UACR (r = -0.29, P < 0.01). Linear regression analysis showed CRAE was associated with UACR in the patients with hypertension(β = -5.0, P < 0.01). Logistic regression analysis showed, systolic blood pressure (β = 1.08, P = 0.02) was risk factor for CRAE abnormality. The CRAE abnormality was increased in turn in the normal control group, normoalbuminuria with the essential hypertension group and microalbuminuria with essential hypertension group (P < 0.01)., Conclusion: The reduction of central retinal artery diameter are associated with the hypertensive renal damage. UACR and CRAE could be used to evaluate the microvascular lesions and be used as an indicator to assess the target organs damage in essential hypertension patients.

In this study, we have introduced an accurate retinal images registration method using affine moment invariants (AMI's) which are the shape descriptors. First, some closed-boundary regions are extracted in both reference and sensed images. Then, AMI's are computed for each of those regions. The centers of gravity of three pairs of regions which have the minimum of distances are selected as the control points. The region matching is performed by the distance measurements of AMI's. The evaluation of region matching is performed by comparing the angles of three triangles which are built on these three-point pairs in reference and sensed images. The parameters of affine transform can be computed using these three pairs of control points. The proposed algorithm is applied on the valid DRIVE database. In general (for the case, each sensed image is produced by rotating, scaling, and translating the reference image with different angles, scale factors, and translation factors), the success rate and accuracy is 95 and 96 %, respectively.

The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree.

Purpose: The purpose of this study is to quantify the normal retinal thickness (RT) and retinal nerve fiber layer thickness (RNFLT), and to obtain cross-sectional area measurements of the main retinal artery and vein in the rabbit animal model using spectral domain optical coherence tomography (SD-OCT)., Materials and Methods: Fifteen eyes of 15 adult rabbits were used to obtain SD-OCT scans. RT, RNFLT and cross-sectional areas of the main retinal artery and vein were measured with a custom-made software grading tool (OCTOR) on selected B-scans at the edge of the optic nerve head and at 1, 2, 3 and 4 mm from the nerve. Statistical comparisons were made using the analysis of variance test with post hoc comparison., Results: In the nasal and temporal retina, the average RT and RNFLT decreased significantly with eccentricity from the optic disc. There was a statistically significant greater RT and RNFLT at the edge of the optic disc as compared with values at 1, 2, 3 and 4 mm from the disc edge (p < 0.01). Mean cross-sectional area of the primary retinal vein was significantly larger than the retinal artery (p < 0.01)., Conclusions: We have quantified the cross-sectional dimensions of RT, RNFLT and the major retinal vessels in the rabbit retina with SD-OCT. These findings are novel anatomic features of the rabbit retina, which should be considered in any studies using this animal model.

Purpose: To assess the correlation and reproducibility of retinal vascular geometric measurements obtained from two stereo-paired fundus images., Methods: Thirty stereoscopic pairs of color optic disc-centered photographs from the Blue Mountains Eye Study were analyzed. Side-by-side grading was performed by a single grader, using semi-automated computer software to quantify the following retinal geometric parameters: (1) retinal arteriolar/venular caliber (CRAE/CRVE); (2) arteriole-to-venule ratio (AVR); (3) branching angle; and (4) tortuosity. We used Pearson correlation (r), intra-class correlation coefficient (ICC), and Bland-Altman plots to assess within-pair correlation and reproducibility for each parameter measured., Results: Inter- and intra-grader r and ICC were high (all r > 0.90 and ICC > 0.90), except for branching angle (ICCs between 0.69-0.83). There was no significant difference between within-pair means of all retinal vascular geometric parameters, before and after excluding poor quality images. CRAE, CRVE, AVR, and arteriolar and venular tortuosity showed very high within-pair correlation and agreement (all r > 0.80 and all ICC > 0.90 respectively). Arteriolar and venular branching angles demonstrated moderate within-pair correlation (r = 0.65 and r = 0.62, respectively) and within-pair agreement (ICC = 0.76 and ICC = 0.77, respectively)., Conclusions: Use of computer-assisted software to measure retinal vascular geometric parameters from paired fundus images was highly repeatable and is robust to differences in photographic angles of paired stereo images. Such measurements can be applied to evaluate temporal changes in longitudinal studies.

Purpose: We measured oxygen saturation in retinal vessels of healthy eyes to determine the effects of age, sex, and cardiovascular parameters, as well as the reliability of the measurements and topographic differences., Methods: The Oxymap T1 retinal oximeter is based on a fundus camera. It simultaneously captures retinal images at two different wavelengths and estimates retinal vessel oxygen saturation. Mean saturation of main retinal arterioles and venules was measured in 120 healthy individuals aged 18-80 years (median 47 years). Of the 120 participants 44 (37%) were male (49 years) and 76 (63%) female (44 years)., Results: Oxygen saturation was 92.2 ± 3.7% (mean ± SD) in retinal arterioles and 55.6 ± 6.3% in venules. No significant difference in oxygen saturation was found between left and right eyes. The inferotemporal quadrant had lower oxygen saturation in arterioles and venules (P < 0.0001). Arteriolar oxygen saturation was stable with age. Venular oxygen saturation in males decreased by 1.9 ± 0.6% (mean ± SEM) per 10 years of age (P = 0.003) and by 0.7 ± 0.4% in females (P = 0.068). Arteriovenous (AV) difference increased by 1.5 ± 0.5% per 10 years in males (P = 0.004) and 1.0 ± 0.4% (P = 0.007) in females. For every 10 mm Hg increase in ocular perfusion pressure, oxygen saturation in arterioles increased by 0.9 ± 0.4% (P = 0.024) and in venules by 1.2 ± 0.7% (P = 0.075)., Conclusions: Retinal arteriolar oxygen saturation is stable in healthy individuals, while there is a significant decrease in venular oxygen saturation with age in males and a similar trend in females. AV difference increases significantly with age for both sexes. Our study provided normative data for spectrophotometric retinal oximetry in the Caucasian population.

Purpose: To estimate the normal distance from vascular termini to ora serrata in children's eyes., Methods: Clinical records and peripheral fluorescein angiography images of the ora serrata region, taken using scleral indentation and the RetCam system during examination under anesthesia, were retrospectively reviewed from consecutive patients with presumed normal peripheral retinal vasculature. All patients had ocular disease either only in the fellow eye or if in the study eye, to a degree judged not likely to affect peripheral retinal vascular development., Results: The record review identified 33 eyes of 31 patients with presumed normal peripheral vasculature. Mean age at angiography was 3.8 years (range, 2 months to 13 years). Mean area of nonperfusion was 0.9 disk diameters (DD) temporally (range, 1.5-0.5 DD; SD 0.3) and 0.6 DD nasally (range, 1-0.25 DD; SD 0.2)., Conclusions: In children up to 13 years of age, the avascular retina normally extends 1.5 DD or less temporally and 1.0 DD or less nasally from the ora serrata. Conservatively, ≥ 2 DD of nonperfusion, 3 standard deviations more than normal, should be considered abnormal and a sign of peripheral nonperfusion. These data may serve as preliminary indicators of the range of normal when evaluating diseases with retinal vascular abnormalities in children., (Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Purpose: Little data exist detailing the normal cup-to-disc (CD) ratios and arteriole-to-venule (A/V) ratios of school age children. In addition, controversy exists in the literature regarding associations between CD and A/V ratios and visual and biometric parameters. The present study investigates the success rates of obtaining useable optic disc images from the portable Nidek Handheld Non-Mydriatic Fundus Camera (NM-200D) from school-age children and describes the distribution of CD ratios and A/V ratios in children aged 6-7 years of age and 12-13 years of age. In addition, the present study explores associations between CD and A/V ratios and a range of visual function and biometric parameters in children., Methods: Fundus images were obtained from 195 6-7 year old children and 227 12-13 year old children participating in a wider study of visual function in childhood (Northern Ireland Childhood Errors of Refraction Study or NICER). ImageJ software was used to obtain CD and A/V ratios from the digital images. Visual function measures and biometric parameters were also available for all participants including; cycloplegic refractive error, vision, corneal curvature, axial length, height and weight., Results: One hundred and eighty fundus images (92.3%) from the 6-7 year olds and 194 images (85.5%) from the 12-13 year olds children were considered useable. Analysis (one way anova) demonstrated statistically significant differences between CD ratios and A/V ratios between the age groups. Participants aged 12-13 years had larger CD ratios and smaller A/V ratios (mean CD ratio 0.37 ± 0.09, mean A/V ratio 0.75 ± 0.10) than 6-7 year old participants (mean CD ratio 0.30 ± 0.09, mean A/V ratio 0.78 ± 0.12). No significant associations were noted between CD ratios and A/V ratio and any visual, ocular or biometric parameters., Conclusions: The present study provides novel normative data on CD and A/V ratios in UK school age children for clinicians in practice., (Ophthalmic & Physiological Optics © 2011 The College of Optometrists.)

Purpose: The objective of this study is to describe the microvascular network of the normal human retina the d using multifractal geometry., Materials and Method: The multifractal analysis of five digitized retinal images was made with the Image J software, exprf applying the standard box-counting method., Results: The human retinal microvascular network has a multifractal geometry. The generalized fractal dimensions Dq were expressed by the mean value and standard deviation. A comparison with the data from studies performed in the ophthalmologic literature was made., Conclusions: Multifractal characterization of human retinal microvascular network, as a non-invasive technique for the analysis of various aspects of retinal vascular topography can be used as a potential marker for early detection of patients with retinal diseases.

Purpose: To systematically examine the association between ocular biometry and retinal vascular caliber in Singapore Chinese preschoolers aged 48 to 72 months., Methods: A total of 469 Singapore Chinese children aged 48 to 72 months were recruited through the Strabismus, Amblyopia and Refractive Error Study in Singaporean Chinese Preschoolers (STARS) from 2006 to 2008. According to standardized protocols, cycloplegic autorefraction, ocular biometry measurements, and retinal photography were performed. Retinal vascular caliber was measured quantitatively and was summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively. Ocular magnification was corrected by using the Bengtsson formula., Results: The mean retinal arteriolar and venular calibers were 156.08 μm and 219.55 μm in boys, and 161.96 μm and 224.25 μm in girls, respectively. In multiple linear regression adjusted for age, sex, father's education, parental myopia history, mean arterial blood pressure, body mass index, and spherical equivalent, each 1.0 mm increase in axial length was associated with a 3.52 μm decrease in retinal arteriolar caliber (P = 0.023) and a 5.55 μm decrease in retinal venular caliber (P = 0.008). Each 1.00 mm increase in corneal curvature was associated with a 13.79 μm decrease (P = 0.004) in retinal venular caliber., Conclusions: In very young children aged 48 to 72 months, narrower retinal arteriolar and venular caliber was associated with elongated axial length. Narrower retinal venular caliber was associated with larger corneal curvature. This suggests that the major structural correlate of myopia might have an effect on retinal microvasculature from early childhood.

A decreased ratio of the width of retinal arteries to veins [arteriolar-to-venular diameter ratio (AVR)], is well established as predictive of cerebral atrophy, stroke and other cardiovascular events in adults. Tortuous and dilated arteries and veins, as well as decreased AVR are also markers for plus disease in retinopathy of prematurity. This work presents an automated method to estimate the AVR in retinal color images by detecting the location of the optic disc, determining an appropriate region of interest (ROI), classifying vessels as arteries or veins, estimating vessel widths, and calculating the AVR. After vessel segmentation and vessel width determination, the optic disc is located and the system eliminates all vessels outside the AVR measurement ROI. A skeletonization operation is applied to the remaining vessels after which vessel crossings and bifurcation points are removed, leaving a set of vessel segments consisting of only vessel centerline pixels. Features are extracted from each centerline pixel in order to assign these a soft label indicating the likelihood that the pixel is part of a vein. As all centerline pixels in a connected vessel segment should be the same type, the median soft label is assigned to each centerline pixel in the segment. Next, artery vein pairs are matched using an iterative algorithm, and the widths of the vessels are used to calculate the AVR. We trained and tested the algorithm on a set of 65 high resolution digital color fundus photographs using a reference standard that indicates for each major vessel in the image whether it is an artery or vein. We compared the AVR values produced by our system with those determined by a semi-automated reference system. We obtained a mean unsigned error of 0.06 (SD 0.04) in 40 images with a mean AVR of 0.67. A second observer using the semi-automated system obtained the same mean unsigned error of 0.06 (SD 0.05) on the set of images with a mean AVR of 0.66. The testing data and reference standard used in this study has been made publicly available.

Background: The purpose of this study was to test the reliability of vessel diameter measurements with a newly developed retinal oximeter., Methods: Twelve healthy individuals participated in the study. Retinal images were taken with the Oxymap Retinal Oximeter. Diameters of retinal vessels were measured automatically with the Oxymap Analyzer software. Repeated measurements on the same vessel segments were compared. The automatic measurements were also compared with semi-automatic measurements with a plug-in for the ImageJ software., Results: Variance coefficient (standard deviation/mean) from the repeatability test was 2.8 and 4.0% for first- and second-degree venules and 3.5 and 5.4% for first- and second-degree arterioles, respectively. ImageJ measured larger mean diameters than Oxymap Analyzer in all cases. Means of differences were 5.1 ± 2.2, 2.9 ± 1.3, and 2.7 ± 1.6 pixels for first-, second-, and third-degree venules and 3.1 ± 1.2, 2.7 ± 0.9, and 2.9 ± 1.4 pixels for first-, second-, and third-degree arterioles., Conclusions: Vessel diameter measurements with the oximeter are repeatable and comparison with an established method demonstrates a relatively stable offset where the standard deviation of the difference is rather small. Different definitions of vessel borders may be the cause of this difference.

An automated method for measurement of arteriolar-to-venular diameter ratio (AVR) is presented. The method includes optic disc segmentation for the determination of the AVR measurement zone, retinal vessel segmentation, vessel classification into arteries and veins, selection of major vessel pairs, and measurement of AVRs. The sensitivity for the major vessels in the measurement zone was 87%, while 93% of them were classified correctly into arteries or veins. In 36 out of 40 vessel pairs, at least parts of the paired vessels were correctly identified. Although the average error in the AVRs with respect to those based on the manual vessel segmentation results was 0.11, the average error in vessel diameter was less than 1 pixel. The proposed method may be useful for objective evaluation of AVRs and has a potential for detecting focal arteriolar narrowing on macula-centered screening fundus images., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

PURPOSE. The aim of this study was to examine the relationship of physical activity and television (TV) viewing time with retinal vascular caliber in a multiethnic Asian population. METHODS. Chinese, Indian, and Malay participants (n = 3866) were examined cross-sectionally in the Singapore Prospective Study Program (2004-2007). Leisure-time physical activity and TV viewing time were assessed by the use of an interviewer-administered questionnaire. Retinal arteriolar and venular calibers were measured from digital retinal photographs. RESULTS. After adjusting for demographic, behavioral, and medical factors, those in the lowest quartile of leisure-time physical activity had a wider venular caliber (by 1.51 μm; 95% confidence interval [CI], 0.01-2.92) compared with those in the highest quartile. Using sex- and ethnicity-specific quartiles, stronger associations were noted in males (2.23 μm; 95% CI, 0.10-4.38) and Chinese (2.52 μm; 95% CI, 0.44-4.59) participants. Females who watched >2 hours of TV per day had a narrow arteriolar caliber (by 1.28 μm; 95% CI, -2.56--0.03), compared with the arteriolar caliber of those who watched less TV. CONCLUSIONS. Lower physical activity and higher TV viewing time (in females) were adversely associated with retinal microvascular caliber among Asian adults. Additional cross-sectional and longitudinal studies are needed to further clarify the potential mediating role of the microvasculature in the relationship between these behavioral risk factors and poor cardiometabolic health outcomes.

Purpose: To evaluate the reproducibility of ImageJ software in analyzing the color of the optic disc., Methods: One hundred twelve normal participants (56 males and 56 females) were enrolled in this study. The image of the optic disc was taken using Kowa digital disc photo-graphy, and the gray scales of the nasal rim (NR), brightest cupping center (BCC) and largest inferior retinal vein (IRV) were calculated using histogram in ImageJ. Three different observers calculated the gray scales three separate times. Reproducibility was assessed using the interclass correlation coefficient (ICC)., Results: The mean age of the participants was 50.6 years old (range, 11 to 82 years). The mean gray scales of the nasal rim were 91.81, 94.91, and 93.24; those of the brightest cupping center were 174.84, 179.94, and 177.76; and those of the largest inferior retinal vein were 61.85, 53.48, and 56.73 for observers 1, 2, and 3, respectively. Inter-observer reproducibility for NR, BCC and IRV was considered good based upon ICC values of 0.944, 0.860, and 0.789 for observers 1, 2, and 3, respectively. Significant age-related differences between the values of the brightest cupping center were noted, and the gray scale score was decreased in the older participants (p < 0.001)., Conclusions: The gray scale of the brightest cupping center diminished with age. ImageJ can be a useful objective tool with high reproducibility in the analysis of optic disc color.

Purpose: Retinal arteriolar and venular calibers are highly heritable and associated with cardiovascular disease. This study was designed to investigate the relative influence of genetic and environmental factors on the high phenotypic correlation (r = 0.59) between these two traits and to assess the shared and specific influence of established and novel cardiovascular disease risk factors on them., Methods: A total of 1463 Caucasian female twins (706 monozygotic and 757 dizygotic), between 24 and 79 years of age, underwent retinal photography from which retinal arteriolar (mean, 153.75 ± 22.1 μm, SD) and venular (mean, 232.1 ± 36.6 μm) calibers were measured with semiautomated software. A bivariate heritability model was used to assess the genetic and environmental influences underlying both specific trait variance and the covariance between the vessel traits. The investigation was an assessment of phenotypic associations between retinal arteriolar and venular calibers and cardiovascular disease risk factors., Results: Additive genetic factors accounted for approximately three fourths of the covariance between retinal arteriolar and venular calibers within the cohort. This finding was replicated in a sample of 1981 twins from the Australian Twins Eye Study. The partial correlation showed that known risk factors accounted for only 5% of the covariance between arteriolar and venular calibers. Novel associations were found between venular caliber and β-cell function (P = 0.011) and insulin sensitivity (P = 0.002)., Conclusions: These results suggest that future gene-mapping studies may identify pleiotropic genetic variants influencing both retinal arteriolar and venular calibers. Genetic variants associated with retinal caliber and (risk factors for) cardiovascular disease should provide new etiologic insights into this complex disease.

Purpose: In the last decades, various analysis methods with different degrees of effectiveness were proposed in medical imaging. Fractal analysis is a mathematical technique that can quantify the degree of complexity and optimality of vascular networks geometry. The objective of this study is to determine the fractal dimension, applying a new standardized protocol for normal vascular network of the human retina using fractal analysis., Materials and Method: The digitized images of the normal vascular network of the human retina were processed and evaluated with the Image J fractal analysis software and the fractal dimensions of normal retinal vascular network were calculated using the standard box-counting method., Results: The central tendency and dispersion measure of fractal dimension were expressed by the mean value and standard deviation. The mean fractal dimension of normal arteriovenous retinal vascular network was 1.698 +/- 0.003. A comparison with the data from studies performed in the ophthalmologic literature was made., Conclusions: The retinal vascular fractal dimension is a noninvasive prediction tool that assist researchers and clinicians for early detection of pacients with different retinal vascular diseases.

Purpose: Retinal blood vessel diameter and arteriovenous ratio (AVR) are commonly used diagnostic parameters. Because vascular walls are typically not visible in funduscopy, clinical AVR estimation is based on the lumen rather than the entire vessel diameter. Here the authors used a transgenic mouse model to quantify AVR in vivo based on total vessel dimensions (wall and lumen)., Methods: Confocal scanning laser ophthalmoscopy (cSLO) and indocyanine green angiography of the retinal vasculature were performed in wild-type and transgenic mice expressing green fluorescent protein (GFP) under the transcriptional control of the smooth muscle type α-actin (αSMA) promoter. Spectral-domain-OCT and ERG were performed to control for integrity of retinal structure and function in vivo and histology to demonstrate the location of GFP expression., Results: Native cSLO imaging and angiography yielded only inner vessel diameters similar to those observed through clinical funduscopy. In αSMA-GFP mice, autofluorescence imaging of the GFP-marked vascular walls also allowed the determination of outer vessel diameters. The mean AVR based on either inner diameter (AVR(id) = 0.72 ± 0.08) or outer diameter (AVR(od) = 0.97 ± 0.09) measurements were significantly different (P < 0.01)., Conclusions: Transgenic αSMA-GFP expression in murine vessel wall components allowed quantification of retinal vessel outer diameters in vivo. Although arterioles and venules differ in lumen and vessel wall width, they share a common outer diameter, leading to an AVR(od) close to unity. Because vessel walls are primary targets in common hypertensive and metabolic diseases, αSMA-GFP transgenic mice may prove valuable in the detailed assessment of such disorders in vivo.

Objective: To describe a new computer-assisted method to measure retinal vascular caliber over an extended area of the fundus., Methods: Retinal photographs taken from participants of the Singapore Malay Eye Study (n = 3280) were used for this study. Retinal vascular caliber was measured and summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) using a new semi-automated computer-based program. Measurements were made at the Standard zone (from 0.5 to 1.0 disk diameter) and an Extended zone (from 0.5 to 2.0 disk diameter)., Results: Reliability of retinal vascular caliber measurement was high for the new Extended zone (intraclass correlation coefficients >0.90). Associations of CRAE with blood pressure were identical between the Extended and Standard zones (linear regression coefficient -2.53 vs. -2.61, z-test between the two measurements, p = 0.394). Associations of CRAE and CRVE with other cardiovascular risk factors were similar between measurements in the two zones. The R² of regression models for the Extended zone was slightly higher than that for the Standard zone for both CRAE (R², 0.324 vs. 0.288) and CRVE (R², 0.325 vs. 0.265)., Conclusions: The new measures from Extended zone are comparable with the previous measures, and also more representative of retinal vascular caliber., (© 2010 John Wiley & Sons Ltd.)

Objectives: This study aims to compare retinal vessel anatomy of normal rhesus monkeys and humans and to provide a basis from a structural perspective for the use of rhesus monkey as an experimental model in future studies of retinal vessels., Methods: The retinas of six normal rhesus monkey eyes and eight human eyecups following corneal transplantation were obtained and stained using adenosine diphosphatase methods. The distributions, orders, layers of the retinal vessels and the perifoveal vascular ring were compared., Results: With adenosine diphosphatase staining, distinct retinal vessels were fully discernable from the first order surrounding the optic disc to the fifth order. There were no statistically significant differences between rhesus monkeys and humans in the percentages of vessels surrounding the optic disc at the equator and the peripheral region. Vascular networks in both species were arranged in several layers around the optic disc, two anastomotic layers at the equator and one sparse layer peripherally. Capillaries at the macular area were quite dense and an intact perifoveal vascular ring was observed. No differences were observed between rhesus monkeys and humans in the percentage area of the vessels and the area, perimeter and diameter of the perifoveal vascular ring., Conclusions: The distributions, orders, layers and the perifoveal vascular ring of the retinal vessels of rhesus monkey are quite similar to those of humans. The data suggest that from an anatomical perspective, the rhesus monkey is a good animal model for the study of human retinal vessels, particularly the macular capillaries.

Purpose: To determine if adjusting for blood vessel (BV) location can decrease the intersubject variability of retinal nerve fiber layer (RNFL) thickness measured with optical coherence tomography (OCT)., Subjects and Methods: One eye of 50 individuals with normal vision was tested with OCT and scanning laser polarimetry (SLP). The SLP and OCT RNFL thickness profiles were determined for a peripapillary circle 3.4 mm in diameter. The midpoints between the superior temporal vein and artery (STva) and the inferior temporal vein and artery (ITva) were determined at the location where the vessels cross the 3.4 mm circle. The average OCT and SLP RNFL thicknesses for quadrants and arcuate sectors of the lower and upper optic disc were obtained before and after adjusting for BV location. This adjustment was carried out by shifting the RNFL profiles based upon the locations of the STva and ITva relative to the mean locations of all 50 individuals., Results: Blood vessel locations ranged over 39 (STva) and 33 degrees (ITva) for the 50 eyes. The location of the leading edge of the OCT and SLP profiles was correlated with the location of the BVs for both the superior [r=0.72 (OCT) and 0.72 (SLP)] and inferior [r=0.34 and 0.43] temporal vessels. However, the variability in the OCT and SLP thickness measurements showed little change due to shifting. After shifting, the difference in the coefficient of variation ranged from -2.1% (shifted less variable) to +1.7% (unshifted less variable)., Conclusions: The shape of the OCT and SLP RNFL profiles varied systematically with the location of the superior and inferior superior veins and arteries. However, adjusting for the location of these major temporal BVs did not decrease the variability for measures of OCT or SLP RNFL thickness.

Purpose: To describe the normal physiological relationship between retinal arteriolar and venular caliber and retinal nerve fiber layer (RNFL), macular, and optic nerve head parameters., Methods: The Sydney Childhood Eye Study assessed 2038 adolescents aged 12 years. Retinal vessel calibers were measured from digital fundus photographs using standardized protocols. Optical coherence tomography measurements of RNFL, macular, and optic nerve head parameters were obtained with the Fast-scan protocol of the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA). Mixed model analyses were performed., Results: After adjustment for covariates, each micrometer increase in RNFL thickness was associated with a 0.22-microm (0.15%, P < 0.0001) and 0.49-microm (0.23%, P < 0.0001) increase in mean arteriolar and venular caliber, respectively. This positive association existed across all RNFL quadrants (0.07%-0.24%, P

The caliber of the retinal vessels has been shown to be associated with stroke events. However, the consistency and magnitude of association, and the changes in predicted risk independent of traditional risk factors, are unclear. To determine the association between retinal vessel caliber and the risk of stroke events, the investigators combined individual data from 20,798 people, who were free of stroke at baseline, in 6 cohort studies identified from a search of the Medline (National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) databases. During follow-up of 5-12 years, 945 (4.5%) incident stroke events were recorded. Wider retinal venular caliber predicted stroke (pooled hazard ratio = 1.15, 95% confidence interval: 1.05, 1.25 per 20-micron increase in caliber), but the caliber of retinal arterioles was not associated with stroke (pooled hazard ratio = 1.00, 95% confidence interval: 0.92, 1.08). There was weak evidence of heterogeneity in the hazard ratio for retinal venular caliber, which may be attributable to differences in follow-up strategies across studies. Inclusion of retinal venular caliber in prediction models containing traditional stroke risk factors reassigned 10.1% of people at intermediate risk into different, mostly lower, risk categories.

Aim: To measure total retinal blood flow in normal human eyes using Doppler Fourier-domain optical coherence tomography (FD-OCT)., Methods: 10 normal people aged 35 to 69 years were measured for the right eye using Doppler FD-OCT. Double circular scans around the optic nerve heads were used. Four pairs of circular scans that transected all retinal branch vessels were completed in 2 s. Total retinal blood flow was obtained by summing the flows in the branch veins. Measurements from the eight scans were averaged. Veins with diameters >33 microm were taken into account., Results: Total retinal blood flow could be measured in eight of 10 subjects: mean (SD) = 45.6 (3.8) microl/min (range 40.8 to 52.9 microl/min). The coefficient of variation for repeated measurements was 10.5%. Measured vein diameters ranged from 33.3 to 155.4 mum. The averaged flow speed was 19.3 (2.9) mm/s, which did not correlate with vessel diameter. There was no significant difference between flows in the superior and inferior retinal hemispheres., Conclusions: Double circular scanning using Doppler FD-OCT is a rapid and reproducible method to measure total retinal blood flow. These flow values are within the range previously established by laser Doppler flowmetry.

Objective: The superior ophthalmic vein (SOV) provides an alternative venous access for the treatment of carotid-cavernous fistulae. Its direct surgical exposure and cannulation can be difficult. This study was performed to identify anatomic landmarks to facilitate localization and exposure of the SOV., Methods: The vascular tree of 6 formalin-fixed human cadaveric heads was injected with colored silicone. The SOV was exposed using a periorbital incision. The diameter of the SOV, its distance to the inferior border of the incision, and the angle formed by the SOV and sagittal midpupillary line were measured. The tributaries of the SOV and its orbital anatomy and relationship to the supraorbital notch/foramen were evaluated., Results: The SOV was located in the superomedial quadrant of the orbit. Its mean diameter was 2.2 mm (standard deviation, +/-1.2 mm). The mean distance from the SOV to the superior sulcus of the eyelid nasally was 5.9 mm (standard deviation, +/-2.0 mm). The mean angle formed by the SOV and the sagittal midpupillary line was 27.9 degrees (standard deviation, +/-5.4 degrees). The tributaries of the SOV were the angular vein and supraorbital vein (SPOV). The SPOV, identified in all 12 dissections, could be followed to the SOV within the orbit. The SPOV was always located inside the supraorbital notch/foramen when the latter was present., Conclusion: The SOV is located at the superomedial quadrant of the orbit. The SPOV is a reliable reference during surgical exposure. A lid crease or subbrow incision centered over the supraorbital notch simplifies identification of the SOV.