Fluorescein Angiography of Floating Retinal Veins.

This case report describes a diagnosis of floating retinal veins in a patient aged 4 years with a history of stage 2 familial exudative vitreoretinopathy.

Retinal artery to vein ratio is associated with cerebral microbleeds in individuals with type 1 diabetes.

OBJECTIVES: A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D. METHODS: We included 146 neurologically asymptomatic individuals with T1D [51% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images. RESULTS: Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs ( P  = 0.023). AVR was inversely associated with the amount of CMBs ( r  = -0.063, P  = 0.035). CMB prevalence was higher in those with AVR below the median (31%) compared with above the median (16%, P  < 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16%, P  = 0.005). A correlation between blood pressure and CRAE ( r  = -0.19, P  = 0.025) appeared among those with T1D. CONCLUSION: Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D.

Absolute retinal blood flow in healthy eyes and in eyes with retinal vein occlusion.

PURPOSE: To measure non-invasively retinal venous blood flow (RBF) in healthy subjects and patients with retinal venous occlusion (RVO). METHODS: The prototype named AO-LDV (Adaptive Optics Laser Doppler Velocimeter), which combines a new absolute laser Doppler velocimeter with an adaptive optics fundus camera (rtx1, Imagine Eyes®, Orsay, France), was studied for the measurement of absolute RBF as a function of retinal vessel diameters and simultaneous measurement of red blood cell velocity. RBF was measured in healthy subjects (n = 15) and patients with retinal venous occlusion (RVO, n = 6). We also evaluated two softwares for the measurement of retinal vessel diameters: software 1 (automatic vessel detection, profile analysis) and software 2 (based on the use of deep neural networks for semantic segmentation of vessels, using a M2u-Net architecture). RESULTS: Software 2 provided a higher rate of automatic retinal vessel measurement (99.5 % of 12,320 AO images) than software 1 (64.9 %) and wider measurements (75.5 ± 15.7 µm vs 70.9 ± 19.8 µm, p < 0.001). For healthy subjects (n = 15), all the retinal veins in one eye were measured to obtain the total RBF. In healthy subjects, the total RBF was 37.8 ± 6.8 µl/min. There was a significant linear correlation between retinal vessel diameter and maximal velocity (slope = 0.1016; p < 0.001; r2 = 0.8597) and a significant power curve correlation between retinal vessel diameter and blood flow (3.63 × 10-5 × D2.54; p < 0.001; r2 = 0.7287). No significant relationship was found between total RBF and systolic and diastolic blood pressure, ocular perfusion pressure, heart rate, or hematocrit. For RVO patients (n = 6), a significant decrease in RBF was noted in occluded veins (3.51 ± 2.25 µl/min) compared with the contralateral healthy eye (11.07 ± 4.53 µl/min). For occluded vessels, the slope between diameter and velocity was 0.0195 (p < 0.001; r2 = 0.6068) and the relation between diameter and flow was Q = 9.91 × 10-6 × D2.41 (p < 0.01; r2 = 0.2526). CONCLUSION: This AO-LDV prototype offers new opportunity to study RBF in humans and to evaluate treatment in retinal vein diseases.

Autonomous Stabilization of Retinal Videos for Streamlining Assessment of Spontaneous Venous Pulsations.

Spontaneous retinal Venous Pulsations (SVP) are rhythmic changes in the caliber of the central retinal vein and are observed in the optic disc region (ODR) of the retina. Its absence is a critical indicator of various ocular or neurological abnormalities. Recent advances in imaging technology have enabled the development of portable smartphone-based devices for observing the retina and assessment of SVPs. However, the quality of smartphone-based retinal videos is often poor due to noise and image jitting, which in return, can severely obstruct the observation of SVPs. In this work, we developed a fully automated retinal video stabilization method that enables the examination of SVPs captured by various mobile devices. Specifically, we first propose an ODR Spatio-Temporal Localization (ODR-STL) module to localize visible ODR and remove noisy and jittering frames. Then, we introduce a Noise-Aware Template Matching (NATM) module to stabilize high-quality video segments at a fixed position in the field of view. After the processing, the SVPs can be easily observed in the stabilized videos, significantly facilitating user observations. Furthermore, our method is cost-effective and has been tested in both subjective and objective evaluations. Both of the evaluations support its effectiveness in facilitating the observation of SVPs. This can improve the timely diagnosis and treatment of associated diseases, making it a valuable tool for eye health professionals.

Retinal venular vessel diameters are smaller during ten days of bed rest.

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m-2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.

Aberrant filling of the retinal vein on fluorescein angiography in branch and hemi-central retinal artery occlusion.

OBJECTIVE: To study aberrant filling of the retinal vessels on fluorescein angiography (FA) images in patients with branch (BRAO) or hemi-central retinal artery occlusions (hemi-CRAO) and correlate with associated changes on optical coherence tomography (OCT). METHODS: Cases of acute BRAO or hemi-CRAO having FA and OCT images at presentation between June 2017 to May 2022 were included. Comparisons were made between the cases with and without aberrant filling of the retinal vessel. RESULTS: Thirty-nine eyes of 39 patients with acute retinal artery occlusions underwent FA and OCT imaging. Seven of the ten cases with either BRAO or hemi-CRAO showed aberrant filling of the retinal vein on FA. No case with CRAO showed aberrant filling on FA. The cases with aberrant filling showed a better presenting visual acuity and lesser severity of retinal ischemia on OCT. Shunts between the retinal artery in the unaffected region and the retinal vein in the affected segment was seen in two eyes. The remaining five eyes showed no arteriovenous anastomosis. Cases with aberrant filling had a better visual function even at the last visit. CONCLUSION: Aberrant retinal vein filling across the horizontal median raphe in the affected region in BRAO or hemi-CRAO eyes had less severity of retinal ischemia and better presenting and final visual acuities. Reduced perfusion in retinal capillaries with altered retinal vascular anatomy or arteriovenous shunts could be probable reasons for the development of this FA finding. Presence of aberrant filling of the retinal vein could indicate better final visual prognosis.

Ultra-Widefield Indocyanine Green Angiography Reveals Patterns of Choroidal Venous Insufficiency Influencing Pachychoroid Disease.

Purpose: To compare patterns of choroidal venous drainage in eyes with pachychoroid disease to those of healthy subjects using ultra-widefield indocyanine green angiography (UWF ICGA). Methods: Patients with pachychoroid disease and healthy controls were recruited at two referral centers. UWF ICGA images were used to evaluate the proportion of the postequatorial fundus drained by major vortex vein systems in each quadrant and to study the incidence and topography of choroidal vascular hyperpermeability (CVH) and intervortex venous anastomoses. Widefield swept-source optical coherence tomography (SS-OCT) was used to evaluate choroidal thickness at the posterior pole in eyes with pachychoroid disease. Results: Fifty-two pachychoroid eyes and 26 healthy eyes were evaluated. Eyes with pachychoroid disease showed a significant within-subject variance in the proportion of the postequatorial fundus drained by each vortex vein system (range, 4.1%-48.1%; P < 0.0001) that was not seen in controls (range, 17.3%-31.7%; P = 0.11). CVH was present in all pachychoroid disease eyes and three of 26 controls. Intervortex venous anastomoses were present in 46 of 52 pachychoroid disease eyes and nine of 26 control eyes. Vortex vein systems with large drainage areas showed greater density of CVH spots. SS-OCT demonstrated asymmetric choroidal drainage in the macula of 59% of pachychoroid eyes. CVH and intervortex venous anastomoses were more prominent in areas showing maximal choroidal thickness. Conclusions: In eyes with pachychoroid disease, imbalanced choroidal venous drainage with congestion of specific vortex vein systems may contribute to a state of choroidal venous insufficiency characterized by regional choroidal thickening, CVH and remodeling of venous drainage routes.

Force and Velocity Based Puncture Detection in Robot Assisted Retinal Vein Cannulation: In-Vivo Study.

OBJECTIVE: Retinal vein cannulation is a technically demanding surgical procedure and its feasibility may rely on using advanced surgical robots equipped with force-sensing microneedles. Reliable detection of the moment of venous puncture is important, to either alert or prevent the clinician from double puncturing the vessel and damaging the retinal surface beneath. This paper reports the first in-vivo retinal vein cannulation trial on rabbit eyes, using sensorized metal needles, and investigates puncture detection. METHODS: We utilized total of four indices including two previously demonstrated ones and two new indices, based on the velocity and force of the needle tip and the correlation between the needle-tissue and tool-sclera interaction forces. We also studied the effect of detection timespan on the performance of detecting actual punctures. RESULTS: The new indices, when used in conjunction with the previous algorithm, improved the detection rate form 75% to 92%, but slightly increased the number of false detections from 37 to 43. Increasing the detection window improved the detection performance, at the cost of adding to the delay. CONCLUSION: The current algorithm can supplement the surgeons' visual feedback and surgical judgment. To achieve automatic puncture detection, more measurements and further analysis are required. Subsequent in-vivo studies in other animals, such as pigs with their more human like eye anatomy, are required, before clinical trials. SIGNIFICANCE: The study provides promising results and the criteria developed may serve as guidelines for further investigation into puncture detection in in-vivo retinal vein cannulation.

Variability of Retinal Vessel Tortuosity Measurements Using a Semiautomated Method Applied to Fundus Images in Subjects With Papilledema.

Purpose: To develop methods to quantitatively measure retinal vessel tortuosity from fundus images acquired in subjects with papilledema and assess sources of variability in these measurements. Methods: Digital fundus images from 30 eyes of subjects with untreated idiopathic intracranial hypertension and papilledema were analyzed. Retinal vein and artery tortuosities for three to four vessels of each type were measured in a region of interest 1.8 to 2.7 mm from the center of the optic nerve head. Measurements were averaged to generate a venous tortuosity index (VTI) and arterial tortuosity index (ATI) for each eye. One image of each eye was analyzed two times by the same rater. Two images of each eye, differing by focal depth, were analyzed by the same rater. Correlations between VTI and ATI for the same image and different images were calculated. Results: Intrarater Pearson correlations (r) were 0.8 (95% confidence interval [CI], 0.59-0.9) and 0.90 (95% CI, 0.73-0.96) for VTI and ATI, respectively, with one outlier removed. Interimage r values were 0.72 (95% CI, 0.48-0.87) and 0.96 (95% CI, 0.89-0.99) for VTI and ATI, respectively, with one outlier removed. The intraclass correlation coefficients for agreement and consistency were similar, suggesting that the discrepancy between measurements was due to residual random error. Conclusions: The finding of similar intrarater and interimage variability suggests that intrarater variability may be a more dominant source than physiology and image acquisition. Translational Relevance: Standardizing rater procedures and averaging multiple measuring sessions are strategies to reduce variability and improve reliability of detecting retinal vessel tortuosity changes in images of eyes with papilledema.

Comparison of Static Retinal Vessel Caliber Measurements by Different Commercially Available Platforms.

SIGNIFICANCE: Commercially available platforms show good agreement in clinical outcomes for retinal vessel caliber measurements, despite differing absolute values. Tighter agreement is observed when right and left eye data are averaged, suggesting an approach suitable for clinical practice. PURPOSE: The purpose of this study was to compare the retinal vessel caliber measurements generated by different commercially available platforms and their associations with systemic blood pressure and age. METHODS: A total of 209 participants were recruited from a UK optometric practice. After a routine eye examination, participants had disc-centered retinal photographs and systemic blood pressure taken. Retinal vessel calibers (central retinal artery equivalent, central retinal vein equivalent, and arteriovenous ratio) were calculated using both MONA REVA and VesselMap. RESULTS: An inverse Pearson correlation was observed between central retinal artery equivalent and mean arterial blood pressure on both platforms (r = -0.275 [P ≤ .001] and r = -0.388 [P ≤ .001] for MONA REVA and VesselMap, respectively); this correlation was also observed with arteriovenous ratio and blood pressure. An inverse correlation was observed between central retinal artery equivalent and age (r = -0.362 [P ≤ .001] and r = -0.404 [P ≤ .001] for MONA REVA and VesselMap, respectively); this was also seen between central retinal vein equivalent and age (r = -0.322 [P ≤ .001] and r = -0.369 [P ≤ .001]). Arteriovenous ratio remained independent from age for both platforms. Bland-Altman plots demonstrated good agreement between the platforms for all three variables. CONCLUSIONS: Although absolute caliber measurements differed between the platforms, the correlations observed were of similar magnitudes, with good agreement between the two platforms. Tighter spaced limits of agreement were observed when right and left eye data were averaged for each subject. In the absence of localized ocular pathology, this approach should be used.

Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography.

This study aimed to theoretically identify the vascular nature of the deep capillary plexus (DCP) by examining patients presenting with both paracentral acute middle maculopathy (PAMM) and prominent middle limiting membrane (p-MLM) sign and p-MLM sign alone in spectral-domain optical coherence tomography (SD-OCT). A retrospective review of the medical records of patients with retinal vein or artery occlusion from two tertiary medical centers was performed. Consecutive patients with a clinical diagnosis of all categories of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) (branch or central and ischemic or non-ischemic) who had undergone SD-OCT imaging from January 2015 to May 2020 were recruited and their p-MLM signs and PAMM lesions were assessed. We included 118 patients who presented with p-MLM sign with or without PAMM lesions. Amon them, 40 were female and 78 were male, with a mean age of 61.1 years. Of the 109 patients with both p-MLM sign and PAMM lesions, 23 had branch RAO, two had branch RVO, 67 had central RAO, 13 had central RVO, and four had a combination of central RAO and central RVO. All nine patients with the p-MLM sign alone had central RVO accompanied by cystoid macular edema. In all the enrolled patients, the hyperreflective lines of the p-MLM sign were continuous, regardless of the type of PAMM lesions. In conclusion, when PAMM and p-MLM sign are examined together, further proof regarding the possible complete venous nature of the vasculature of the retinal DCP might be speculated.

[Venous blood flow in ocular vessels of patients with active retinopathy of prematurity]. / Osobennosti venoznogo krovotoka v sosudakh glaza pri aktivnoi retinopatii nedonoshennykh.

PURPOSE: To study the characteristics of venous circulation in the eyes with retinopathy of prematurity (ROP) observed in examination of blood flow in the central retinal vein and superior orbital vein in patients with different forms, stages and state of the disease. MATERIAL AND METHODS: Color duplex scanning of the central retinal vein and superior orbital vein was performed using color Doppler imaging and pulsed Doppler sonography in 55 premature babies (55 eyes) with active ROP and 8 premature babies (8 eyes) with no signs of ROP. All babies included in the study were born at 25-32 weeks of gestation, their birth weight was 680-1760 g. RESULTS: A characteristic feature of hemodynamic parameters in the central retinal vein at stages 1-3 of active ROP was a decrease in both the maximum and minimum blood flow velocities (Vmax and Vmin), indicating a serious disorder of ocular hemodynamics in this category of patients. An increase in Vmax in the central retinal vein was recorded for patients with aggressive posterior ROP, which occurs in response to venous stasis that is common in this form of the disease. The performed statistical assessment of the prognostic significance of hemodynamic parameters of the central retinal vein in relation to the type of active ROP revealed a high information content of Vmin, which is promising for early detection of unfavorable course of the disease helping to ensure timely treatment. The blood flow in the superior orbital vein showed distinctive absence of any correlations with the course of the disease, disallowing any immediate conclusions on the informativeness and predictive value of its parameters. CONCLUSION: The revealed features of venous blood flow in patients with active ROP help expand the understanding of vascular changes in this pathology, and can also be applied in clinical practice to improve the accuracy of predicting the course of the disease.

Pulsation of anastomotic vortex veins in pachychoroid spectrum diseases.

Accumulating evidence points to pachychoroid possibly being caused by vortex vein congestion which results in remodeling of choroidal drainage routes via intervortex vein anastomosis. This hypothesis prompted us to investigate vortex vein hemodynamics by studying videos of indocyanine green angiography (ICGA) in a retrospective case series of 295 eyes with pachychoroid spectrum diseases. In the early phase of the video-ICGA, pulsatile vortex venous flow was observed in 76 eyes (25.8%) at the vortex veins connected with anastomosis between superior and inferior vortex veins. The patients with pulsatile vortex venous flow were significantly older than those without pulsatile vortex venous flow (67.8 ± 13.2 vs. 63.9 ± 14.5 years, P < 0.05). Pulsatile vortex venous flow was 1.84 times more common in the inferior quadrants than in the superior quadrants. Interestingly, 14 of 76 eyes (18.4%) with pulsatile vortex venous flow showed retrograde pulsatile blood flow in the vortex veins. This retrograde pulsatile blood flow was 2.50 times more common in the inferior than in the superior quadrants. These findings indicate altered vortex vein hemodynamics due to vortex vein congestion in pachychoroid spectrum diseases.

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes.

Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes.Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules.Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88-1.17% vs ECG-gated: 0.39, 95%CI 0.29-0.49%, p < .0001) than venular (ungated 0.62, 95%CI 0.53-0.73% vs ECG-gated: 0.26, 95%CI 0.19-0.35%, p < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively.Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.

Comparison of Two Spectral-domain Optical Coherence Tomography Scan Modes for Measuring Retinal Vessel Diameter.

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.

Quantitative evaluations of vortex vein ampullae by adjusted 3D reverse projection model of ultra-widefield fundus images.

The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P < 0.05). The number and location of VVA can be obtained non-invasively, and the number was significantly higher in men than women. This technique can be used to determine whether these values are altered in a retinochoroidal disease.