Liquid-Driven Microinjection System for Precise Fundus Injection.

Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the microinjection procedure is usually performed by using the viscous fluid control of a standard vitrectomy system, which applies a fixed air pressure through foot pedal activation. The injection process with the fixed pressure is uncontrollable and lacks feedback, the high flow rate of the injected drug may cause damage to the fundus tissue. In this paper, a liquid-driven microinjection system with a flow sensor is designed and developed specifically for fundus injection. In addition, a PID sliding mode control (SMC) method is proposed to achieve precise injection in the injection system. The experimental results of fundus simulation injection demonstrate that the microinjection system meets the requirements of fundus injection and reduces the impact of the injection process on the fundus tissue.

Investigation into safflower injection as a prophylactic treatment for retinal vein occlusion in a rabbit model.

The study aimed to assess the effect and mechanism of safflower injection in preventing retinal vein thrombosis in rabbits. Twenty healthy adult pigmented rabbits were randomly assigned to either the experimental group, receiving safflower injection, or the control group, receiving normal saline. After two weeks of treatment, blood samples were collected to analyze platelet adhesion and aggregation rates. Photodynamic therapy was applied to induce occlusion in the target retinal vein. Fundus photography and fluorescein angiography were recorded using a dynamic microscopic monitoring system, and laser speckle imaging was employed to assess blood flow in the affected vein. The experimental group exhibited significantly lower rates of platelet adhesion and aggregation compared to the control group. Following the induction of retinal vein occlusion, the experimental group showed a lower complete occlusion rate of the target retinal vein. Although initial blood flow in the target vein was similar between groups, the blood flow at 1, 3, and 5 min post-occlusion was significantly higher in the experimental group. Safflower injection delayed retinal vein thrombosis formation, preserved blood flow in the affected retinal area, and reduced platelet adhesion and aggregation. These effects facilitated vascular reperfusion within a limited timeframe.

Edge-Guided Contrastive Adaptation Network for Arteriovenous Nicking Classification Using Synthetic Data.

Retinal arteriovenous nicking (AVN) manifests as a reduced venular caliber of an arteriovenous crossing. AVNs are signs of many systemic, particularly cardiovascular diseases. Studies have shown that people with AVN are twice as likely to have a stroke. However, AVN classification faces two challenges. One is the lack of data, especially AVNs compared to the normal arteriovenous (AV) crossings. The other is the significant intra-class variations and minute inter-class differences. AVNs may look different in shape, scale, pose, and color. On the other hand, the AVN could be different from the normal AV crossing only by slight thinning of the vein. To address these challenges, first, we develop a data synthesis method to generate AV crossings, including normal and AVNs. Second, to mitigate the domain shift between the synthetic and real data, an edge-guided unsupervised domain adaptation network is designed to guide the transfer of domain invariant information. Third, a semantic contrastive learning branch (SCLB) is introduced and a set of semantically related images, as a semantic triplet, are input to the network simultaneously to guide the network to focus on the subtle differences in venular width and to ignore the differences in appearance. These strategies effectively mitigate the lack of data, domain shift between synthetic and real data, and significant intra- but minute inter-class differences. Extensive experiments have been performed to demonstrate the outstanding performance of the proposed method.

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.

Narrowing Ratio of Retinal Veins at Arteriovenous Crossing in Patients With Branch Retinal Vein Occlusion Versus That in Healthy Individuals.

Purpose: This cross-sectional study aimed to clarify the differences in the retinal venous narrowing ratio (VNR) at retinal arteriovenous crossing by optical coherence tomography (OCT) among the eyes with branch retinal vein occlusion (BRVO), fellow eyes of patients with BRVO, and eyes of individuals without BRVO and to determine factors that influence the VNR. Methods: We studied 31 eyes of young participants, 54 eyes of an older control group, 56 fellow eyes of patients with BRVO, and 48 eyes with BRVO. Cross-sectional OCT images were used to determine the VNR at two arteriovenous crossings per eye. Results: Overall, 378 arteriovenous crossings were analyzed. The VNR of arterial overcrossings of fellow eyes (27.7% ± 11.1%) and BRVO eyes (27.3% ± 9.76%) were significantly higher than those in the young (16.0% ± 7.9%, all P < 0.001) and control (22.0% ± 8.81%, P < 0.001, P = 0.003, respectively) groups. The VNR of arterial overcrossings was significantly larger than that of venous overcrossings (24.0% ± 10.5% vs. 20.6% ± 13.0%, P = 0.021). A linear mixed-effects model showed that the VNR was significantly higher in arterial overcrossings, crossings with larger arterial internal diameters, smaller venous internal diameters, and participants with older age and a BRVO history. Conclusions: The VNR in arterial overcrossings was higher in BRVO eyes and even in the fellow eyes. Thus, a higher VNR in arterial overcrossings may contribute to BRVO development, and crossings with factors contributing to higher VNR might be associated with a risk of BRVO.

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.

Central retinal vein and artery occlusion associated with sildenafil: a case report and review of the literature.

BACKGROUND: Sildenafil is a selective phosphodiesterase type 5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. It is available over the counter in many countries. While there have been a few reports of retinal vascular occlusion following sildenafil consumption, most cases have other comorbidities as risk factors for the disease, and the exact causal role of this drug in these conditions remains unclear. CASE PRESENTATION: We present the case of a healthy 32-year-old Iranian man who developed combined central retinal vein occlusion and retinal artery occlusion following sildenafil exposure. The patient underwent a hypercoagulative state workup for possible underlying risk factors. Additionally, we conducted a literature search on PubMed using the keywords: retinal vein occlusion AND Sildenafil OR Viagra, retinal artery occlusion AND Sildenafil OR Viagra, retinal vascular occlusion AND Sildenafil OR Viagra. To obtain more objective results in the reviews, we employed an adverse drug reaction possibility algorithm. The patient was found to be otherwise healthy, and ancillary tests were unremarkable. A literature review identified seven reports of retinal vascular occlusion following sildenafil use. In most of these cases, the role of sildenafil was not clearly established. To the best of our knowledge, our case achieved the highest score based on the algorithm compared with previous reports. CONCLUSION: Sildenafil may be associated with severe retinal vascular accidents in otherwise healthy young individuals.

Retinal vein changes in patients with high-risk proliferative diabetic retinopathy treated with conbercept and panretinal photocoagulation co-therapy: a cohort study.

Objective: This study aimed to observe and compare retinal vein diameter changes and other essential indicators in patients with high-risk proliferative diabetic retinopathy (PDR) treated with intravitreal injection of conbercept (IVC) combined with panretinal photocoagulation (PRP) versus PRP monotherapy. Methods: A retrospective analysis was conducted on data from patients with high-risk PDR who received specific treatment and were followed up for 24 months. Among 82 patients with high-risk PDR, 50 eyes received PRP combined with IVC, whereas 32 eyes received PRP alone. During the 24-month follow-up period, changes in best-corrected visual acuity (BCVA), central foveal thickness (CFT), retinal vein diameter, number of microaneurysms (MA), neovascularization (NV) area, hard exudate (HE) area, size of the foveal avascular zone (FAZ), superficial capillary plexus (SCP) blood flow density, and adverse effects were recorded and compared between the two groups at baseline and at 6, 12, 18, and 24 months after treatment. The relationship between each observation index and vein diameter was also analyzed. Results: During the 24-month follow up, significant improvements in the BCVA, CFT, retinal vein diameter, number of MAs, NV area, HE area, FAZ, and SCP were observed in the IVC+PRP group after treatment. The PRP group only showed significant reductions in NV and HE areas. The IVC+PRP group showed significant superiority over the PRP group in improving the vein diameter, number of MA, and HE area. However, no statistically significant difference in NV area reduction was found between the groups. Conclusion: In the treatment of high-risk PDR, IVC+PRP therapy has a significant advantage over PRP monotherapy. IVC+PRP therapy may reverse diabetes-induced retinal vein changes, restoring morphology and function.

Laser-Induced Chorioretinal Anastomosis in Neurofibromatosis Type 1.

This case report describes a laser-induced chorioretinal anastomosis in a 38-year-old woman with neurofibromatosis type 1.

Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction.

This study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex.

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9.5  µm; 95% confidence interval, 8.0-11.1  µm) was larger than the between-device difference in CRVE (2.9  µm; 95% confidence interval, 1.3-4.5  µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4.8 to 23.9  µm for CRAE and -12.0 to 17.8  µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83-0.92) and 0.91 (95% confidence interval, 0.86-0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy.

BACKGROUND: Patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who received at least one intravitreal injection of anti-vascular endothelial growth factor therapy (VEGF) and lost to follow-up (LTFU) for more than six months were analyzed to investigate the factors contributing to the LTFU and the prognosis. METHOD: This was a retrospective, single-center study to analyze the causes and prognosis of LTFU over six months in RVO-ME patients treated with intravitreal anti-VEGF injections at our institution from January 2019 to August 2022 and to collect patients' baseline characteristics along with the number of injections before LTFU, primary disease, best corrected visual acuity (BCVA) before LTFU and after return visit, central macular thickness (CMT), months before LTFU and after LTFU, reasons for LTFU, and complications, to analyze the factors affecting visual outcome at a return visit. RESULTS: This study included 125 patients with LTFU; 103 remained LTFU after six months, and 22 returned after LTFU. The common reason for LTFU was "no improvement in vision" (34.4%), followed by "transport inconvenience" (22.4%), 16 patients (12.8%) were unwilling to visit the clinic, 15 patients (12.0%) had already elected to seek treatment elsewhere, 12 patients (9.6%) were not seen in time due to the 2019-nCov epidemic, and 11 patients (8.8%) cannot do it due to financial reasons. The number of injections before LTFU was a risk factor for LTFU (P < 0.05). LogMAR at the initial visit (P < 0.001), CMT at the initial visit (P < 0.05), CMT before the LTFU (P < 0.001), and CMT after the return visit (P < 0.05) were influential factors for logMAR at the return visit. CONCLUSION: Most RVO-ME patients were LTFU after anti-VEGF therapy. Long-term LTFU is greatly detrimental to the visual quality of patients; thus, the management of RVO-ME patients in follow-up should be considered.

Retinal Periphlebitis May Be a Marker for Subphenotype in Multiple Sclerosis.

Retinal periphlebitis (RPP) is a long-known entity in patients with multiple sclerosis (MS) and has not been revisited in the context of recent developments in MS pathogenesis and heterogeneity. We present six cases of RPP in three female and three male MS patients. They all have relapsing-remitting MS and did not have or had minor ocular symptoms. It is important to perform a thorough retinal examination in patients with MS, as peripheral and sectorial lesions could be unseen. A better knowledge on the concomitant involvement of retinal veins contributes to the understanding of immunopathology, with potentially distinct autoantigenic targets. RPP might serve as a subphenotype marker that may influence treatment choices in MS. Further research is needed.

Quantification of retinal vein and artery trajectories using second-order polynomial equation in eyes with vitreomacular traction.

BACKGROUNDS: To measure the degree of curvature of the retinal artery trajectory (RAT) and retinal vein trajectory (RVT) in the eyes of patients with vitreomacular traction (VMT) and compare them with their healthy fellow eyes. METHODS: This was a retrospective, cross-sectional, case-control study of 58 eyes of 29 patients with unilateral VMT. The participants were divided into two groups. Group 1 VMT was defined as having only morphological changes, while group 2 VMT was defined as morphological changes accompanied by the presence of a cyst or hole to quantify the severity of the disease. The RATs and RVTs were assessed from the color fundus photographs using the ImageJ program. The fundus photographs were rotated 90°. The course of the retinal arteries and veins were marked on a color fundus photograph and fitted to a second-degree polynomial curve (axe[x]/100+bx+c). The coefficient ''a'' was the width and steepness of the trajectories. The comparison between the RAT and RVT of VMT and healthy fellow eyes was investigated and the association between the RAT and RVT and the severity of disease were determined using the Image J program. RESULTS: Eleven subjects were male, and 18 subjects were female. The mean ± SD age was 70.6 ± 7.6 years. Eighteen of the eyes had VMT in the right and 11 of the eyes had VMT in the left eye. Eleven eyes were in group 1 and 18 eyes were in group 2. Axial length (AL) was similar between the two groups (22.63 ± 1.20 mm vs 22.45 ± 1.45 mm p = 0.83) (Table 1). The mean RAT was 0.60 ± 0.18 in eyes with VMT and 0.51 ± 0.17in healthy eyes (p = 0.063). The mean RVT was 0.74 ± 0.24 in eyes with VMT and 0.62 ± 0.25 in healthy eyes for the whole group (p = 0.02). In group 1, the mean RVT of the eyes with VMT was statistically significantly higher than the healthy eyes (p = 0.014). There was not any statistically significant difference for the other parameters evaluated between eyes with VMT and healthy eyes according to the groups and the whole group. (Tables 2-4) CONCLUSION: Unlike other vitreoretinal interface diseases such as epiretinal membrane and macular hole, VMT may be characterized by a narrower RVT, which is characterized by a larger "a" value.

Empirical retinal venous pulse wave velocity using modified photoplethysmography.

OBJECTIVE: Using the novel imaging method of high-speed modified photoplethysmography we measured the retinal venous pulse wave velocity in a single case. RESULTS: A healthy 30-year-old subject underwent high-speed modified photoplethysmography (120 frames per second) with simultaneous ophthalmodynamometry at 26 Meditron units. A video of the optic nerve was analyzed using custom software. A harmonic regression model was fitted to each pixel in the time series and used to quantify the retinal vascular pulse wave parameters. Retinal venous pulsation at the optic disc was observed as a complex dynamic wall motion, whereas contraction commenced at a point in the vein at the center of the optic disc, and progressed centrifugally. The empirically estimated retinal venous pulse wave velocity at this segment was approximately 22.24694 mm/s. This measurement provides an estimate for future studies in the field.