Evaluating Ocular Blood Flow in Diabetic Macular Edema using Three-dimensional Pseudocontinuous Arterial Spin Labeling.

BACKGROUND: Alterations in ocular blood flow play an important role in the pathogenesis of diabetic macular edema; however, this remains unclear. OBJECTIVES: This study aimed to investigate ocular blood flow in eyes with or without diabetic macular edema using arterial spin labeling. METHODS: This cross-sectional study included 118 eyes of 65 patients with diabetic retinopathy analyzed between November 2018 and December 2019. We included a total of 53 eyes without diabetic macular edema (mean [SD] age, 57.83 [7.23] years; 29 men [54.7%]) and 65 eyes with diabetic macular edema (mean [SD] age, 60.11 [7.63] years; 38 men [58.5%]). Using a 3.0-T magnetic resonance imaging, participants were imaged with arterial spin labeling with multiple post-labeling delays. RESULTS: The mean ocular blood flow at post-labeling delays of 1.5 and 2.5 s was significantly lower in eyes with diabetic macular edema among patients with diabetic retinopathy compared with the remaining subgroups (P=0.022 and P <0.001, respectively). The mean ocular blood flow exhibited a significant decrease in eyes with diabetic macular edema when the post-labeling delay was set at 2.5 s in the nonproliferative and proliferative diabetic retinopathy groups, compared with the remaining subgroups (P=0.005 and P=0.002, respectively). The cutoff points of ocular blood flow at post-labeling delays of 1.5 s and 2.5 s were 9.40 and 11.10 mL/100 g/min, respectively. CONCLUSION: Three-dimensional pseudocontinuous arterial spin labeling can identify differences in the ocular blood flow of patients with diabetic eyes with and without diabetic macular edema.

Fluorescent Pdots Facilitate High-Resolution Mapping of the Intact Meningeal Vascular Network and Eye-Brain Connections.

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel. With the help of high-brightness polymer dots (Pdots) as probe, macroscopic and detailed imaging of the vascular network on the intact dorsal meninges can be performed. Meningeal vessels are symmetrically distributed along the superior sagittal sinus, and the distribution of meningeal vessels had a certain degree of hierarchy. The meninges are thicker blood vessels and capillary networks from the outside to the inside. Moreover, the diameter of the capillaries is 3.96 ± 0.89 µm. Interestingly, meningeal primo vessels in the central nervous system of mice is imaged with the diameter of 4.18 ± 1.18 µm, which has not been reported previously. It is worth mentioning that we found that orthotopic xenografts of brain tumors caused the appearance of corneal neovascularization and morphological changes in optic nerve microvessels. In conclusion, our work provides an effective Pdots-based imaging method for follow-up research on meningeal vascular-related diseases, and illustrates that the eye can serve as a window for the prevention and diagnosis of brain diseases.

Effects of switching from intravitreal injection of aflibercept to faricimab on ocular blood flow in patients with diabetic macular edema.

We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with treatment-resistant diabetic macular edema (DME). The medical records of 15 patients with DME who had received IVA injection ≥ 3 months before were retrospectively reviewed. The best-corrected visual acuity, central macular thickness (CMT) on optical coherence tomography, and mean blur rate (MBR) of all disc areas on laser speckle flowgraphy were measured before, 1 week after, and 4 weeks after IVA and IVF, respectively. The changes in visual acuity showed no significant difference after switching from IVA to IVF (P = 0.732). The mean CMT decreased significantly during the follow-up period (both P < 0.001). MBR showed no significant difference during the follow-up period (P = 0.26). However, it decreased significantly 4 weeks after IVF (P = 0.01) compared with the baseline value, but not 4 weeks after IVA (P = 0.074). A significant association was observed between decreased MBR and decreased CMT in patients who received IVF (correlation coefficient: 0.501, P = 0.005) but not in those who received IVA (P = 0.735). Thus, IVF maintained ocular blood flow reduction, although no significant differences in visual acuity and CMT changes were observed compared to IVA.

Melatonin: Unveiling the functions and implications in ocular health.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

Superior Ophthalmic Vein Thrombosis Associated With Asymptomatic COVID-19 Infection.

Superior ophthalmic vein thrombosis is a rare condition scarcely described in clinical literature with potentially severe consequences including permanent vision loss. This report details the case of a 70-year-old woman who presented with acute binocular horizontal diplopia, relative proptosis of the OD by 4 mm, and pain OD. On exam, visual acuity was 20/20 OD and 20/30 OS with full extraocular movements. CT revealed proptosis OD with a thrombosed superior ophthalmic varix. Evaluation for etiology of hypercoagulability was unremarkable, although the patient did have an asymptomatic COVID-19 infection 1 month prior. To the authors' knowledge, this is the first reported case of superior ophthalmic vein thrombosis secondary to an asymptomatic COVID-19 infection.

Superior Ophthalmic Vein Thrombosis: A Case Report in a Previously Healthy Methicillin-Resistant Staphylococcus aureus-Positive Patient.

BACKGROUND Superior ophthalmic vein thrombosis (SOVT) is a rare condition, with an incidence of 3 to 4 cases per million per year. SOVT can be classified according to the underlying etiology into septic or aseptic SOVT. We present a case of right SOVT in a previously healthy patient with a positive blood culture of methicillin-resistant Staphylococcus aureus (MRSA). CASE REPORT A previously healthy 38-year-old female patient presented with a 2-week history of worsening right-sided headache associated with photophobia, phonophobia, right-sided ear pain, and tinnitus. The best corrected visual acuity was 6/12 in the right eye and 6/6 in the left eye. Ophthalmic examination revealed right eye upper lid edema, proptosis, and diplopia in all gazes, mainly vertical. The fundus examination showed a raised hyperemic right optic disc with blurred margins. Laboratory investigations showed a positive blood culture of MRSA and elevated levels of inflammatory markers erythrocyte sedimentation rate and C-reactive protein. Orbital computed tomography examination showed periorbital and orbital cellulitis with superior ophthalmic vein thrombosis. The patient was treated successfully with antibiotics and anticoagulants. At 1-month follow-up, the patient was compliant with medications and reported full resolution of symptoms, with no visual acuity impairment. CONCLUSIONS SOVT is a challenging ophthalmic condition and can be present concurrent with orbital cellulitis or cavernous sinus thrombosis. Early imaging studies and proper management are important to prevent serious complications. Ophthalmologists need to be alerted of the importance of tailoring antibiotics based on the causative agent, to decrease the risk of therapeutic failure and microbial resistance.

Pressure-Lowering Effect of Interventional Fistula Occlusion in Secondary Glaucoma due to Orbital Draining Intracerebral Fistulae. / Drucksenkender Effekt der interventionellen Fistelokklusion bei Sekundärglaukom infolge orbital drainierender intrazerebraler Fisteln.

BACKGROUND: Carotid cavernous sinus fistulas (CSCF) are pathological connections of the internal and/or external carotid artery (and/or its branches) to the cavernous sinus. Ophthalmological symptoms and problems occur particularly when drainage is via the superior ophthalmic vein. MATERIAL AND METHODS: Seven eyes of six patients with a high-grade suspicion of CSCF were included in this retrospective monocentric study. Digital subtraction angiography (DSA) was performed in the included patients, where an interventional fistula closure was performed in the case of CSCF. Four of the six patients received a pre- and post-interventional day-night intraocular pressure profile. Furthermore, medical history, symptoms, visual acuity, slit lamp microscopic findings, and DSA findings were evaluated. RESULTS: The most common symptoms reported by patients were red eyes, diplopia, and exophthalmos. When the intraocular pressure (IOP) was measured, 83.33% of the patients showed increased values. The mean IOP in the day-night intraocular pressure profile in the affected eye before intervention was 23.5 (± 2.7) mmHg compared to 14.1 (± 2.3) mmHg in the healthy eye. A significant difference could thus be demonstrated in side comparison (p = 0.0047). The post-interventional measurement showed a mean IOP of 15.3 (± 1.0) mmHg in the affected eye and thus a significant difference to the pre-interventional measurement in the affected eye (p = 0.0018). Four of the six patients with CSCF were taking antiglaucomatous eye drops before the intervention, and two patients after the intervention. The number of antiglaucoma drugs used could also be reduced. CONCLUSION: Interventional fistula closure is an effective method for treating the secondary increase of IOP in CSCF. Successful closure of the fistula showed a significant reduction in IOP, which was not possible with the sole administration of antiglaucoma drugs. Radius-Maumenee syndrome should be considered as a differential diagnosis.

"A case of ocular ischemic syndrome in spontaneous acute internal carotid dissection: The importance of multidisciplinary management".

AIMS: To emphasize that ocular ischemic syndrome (OIS) is a rare but threatening condition. It is a consequence of occlusion or dissection of internal carotid artery (ICA). METHODS: A 66-year-old caucasian male presented in the emergency room with painful vision loss in his right eye and mild neurological symptoms. He was diagnosed ocular ischemic syndrome (OIS) in ICA and ophthalmic artery occlusion due to right ICA dissection. CONCLUSIONS: It is very important to know and be able to recognise OIS as it may often be misdiagnosed or treated as a different entity. Patients with ICA occlusion and OIS must be treated as soon as possible by a stroke unit team to resolve ICA occlusion/dissection and by the ophthalmologist to prevent further ocular related complications.

Association between resistivity index of central retinal artery and severity of diabetic retinopathy.

Purpose: Diabetic retinopathy (DR) is a leading cause of ocular morbidity. Its progression depends mainly on retinal vasculature and ocular blood flow. Color Doppler imaging (CDI) is a noninvasive imaging technique that measures blood flow velocity. The resistivity index (RI), calculated by the CDI, reflects the vascular resistance distal to the measuring location. RI is independent of the doppler angle and position of the patient, making it a reliable and reproducible parameter. To the best of our knowledge, there is only one study in literature studying the association between resistivity index (RI) of the central retinal artery (CRA) and severity of DR. Aim: To determine the association between RI of CRA and severity of DR. To determine the association between RI of CRA and spectral-domain optical coherence tomography (SD-OCT) biomarkers for DR. Methods: Type II diabetics visiting our OPD underwent DR screening and were graded into three categories according to ETDRS classification which include Group A-No diabetic retinopathy (No DR), Group B-Nonproliferative diabetic retinopathy (Moderate-Severe-Very Severe NPDR), and Group C-Proliferative diabetic retinopathy (PDR). SD-OCT was performed. Ultrasonic color doppler imaging was done. RI of the CRA was noted. It was compared between the three groups and its association with severity of DR and OCT biomarkers (central subfield thickness, cube average thickness and ellipsoid zone disruption) was studied. Results: 56 eyes of 28 patients were included in our study with 20 in Group A,14 in Group B, and 22 in Group C. RI of CRA compared within groups showed statistically significant association with severity of DR (P < 0.001). The presenting BCVA (LogMar) showed positive correlation with RI in all groups. OCT biomarker central subfield thickness showed a positive correlation with RI in Groups A (P < 0.001) and B. Ellipsoid zone (EZ) disruption showed a statistically significant association with RI in Group C (P < 0.001). Conclusion: The RI of CRA is a reliable biomarker for the assessment of the severity of DR. Patients with high RI of CRA had higher chances of EZ disruption and presented with poor visual acuity.

Dilated superior ophthalmic vein: systemic associations.

PURPOSE: To review systemic associations of patients with dilated superior ophthalmic veins (SOV) in the absence of orbital, cavernous sinus, or neurological disease. METHODS: Retrospective review of patients who had dilated SOVs with a diameter of ≥ 5.0 mm. Patients with a dilated SOV secondary to orbital, cavernous sinus or neurological disease were excluded. Patient demographics, past medical history, and SOV diameters on initial and follow up scans were collected. The maximum diameter of the SOV was taken perpendicular to the long axis of the SOV. RESULTS: Nine cases were identified. Patients ranged in age from 58 to 89 years and six out of nine were female. The dilated SOV involved both eyes in two cases, left eye in five cases and right eye in two cases. Three patients had dilated SOV likely secondary to raised venous pressures from decompensated right heart failure (n = 1), pericardial effusion (n = 1) and left ventricle dysfunction secondary to a myocardial infarction (n = 1). Five patients had a significant history of previous ischaemic heart or peripheral vascular disease. Two patients had risk factors for venous clotting disease whilst one patient had a history of giant cell arteritis and vertebral artery dissection. CONCLUSION: A dilated SOV may raise concern for life threatening conditions such as a carotid cavernous fistula and may prompt additional investigations. A dilated SOV may be reversible and secondary to raised venous pressures due to cardiac failure. Other cases may be seen in patients with significant cardiovascular risk factors, possibly due to changes in vasculature.

Assessment interocular symmetry of peripapillary vessel density in young myopes with optical coherence tomographic angiography.

PURPOSE: The purpose of our study was to evaluate the interocular symmetry and distribution of peripapillary vessel density in young myopic eyes. METHODS: A cross-sectional observational study was designed. A total of 174 eyes of 87 young myopic patients were recruited in this study. According to spherical equivalent (SE), 48 eyes were classified as mild myopia with a mean SE of - 2.12D (SD 0.66D), 66 as moderate myopia with a mean SE of - 4.50D (SD 0.87D), and 60 as high myopia with a mean SE of - 7.39D (SD 1.30D). Optical coherence tomography angiography (OCTA) was used to measure the vessel density. The distribution and interocular symmetry of peripapillary vessel densities were analyzed. RESULTS: The vessel densities in the whole image, peripapillary, superior and inferior sectors were significantly lower in the high myopia group than in the mild or moderate myopia group (All P < 0.001), and the density in the nasal sector was significantly lower in the high myopia group than in the mild group. And most interesting, the vessel densities in the inside disc and temporal sector showed no difference among the three myopic groups (All P > 0.05). By Pearson correlation analysis, the vessel densities in the whole image, peripapillary, superior, inferior and nasal sectors were negatively correlated with axial length (AL) and SE (All P < 0.001), but vessel densities in the inside disc and temporal sector did not show this correlation (All P > 0.05). Interocular symmetry was observed in all the vascular parameters through paired-samples t-tests (All P > 0.05), intraclass correlation coefficient (ICC) and Pearson correlation analysis (All P < 0.001). CONCLUSION: The density of radial peripapillary capillaries decreased in the myopic eye with axial elongation, and optical vascular parameters showed significant interocular symmetry among young myopic eyes.

Ex vivo ocular perfusion model to study vascular physiology in the mouse eye.

Several hypotheses have been tested to understand whole organ regulation in other organs such as the brain and kidney, but no such hypothesis has yet been proposed for ocular circulations. To some extent resolve this deficit our ex vivo mouse eye perfusion model takes the first step in elucidating the mechanisms controlling the individual components of the ocular circulation. Various isolated ocular vascular preparations have been utilized in studies of ocular vascular biology, physiology, and pharmacology, including studies on both normal and pathological conditions. However, there is still significant potential for further studies to improve our understanding of ocular circulation and its regulation. The choroid specifically is inaccessible to direct visualization due to the retina's high metabolic requirement with a transparency that cannot be compromised by an overly rich vascular network on the inner retinal side hindering the visualization of the choroid. In this technical paper, we provide a detailed description of all the steps to be followed from the enucleation of mouse eyes to cannulation of the ophthalmic artery and perfusion and ex vivo confocal microscopy imaging of the dynamic nature of the choroid circulation.

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

Purpose: To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes. Methods: Porcine anterior segments (n = 14) were mounted in a perfusion chamber and perfused using Dulbecco's phosphate buffered solution with glucose. Fluorescein angiography was performed to determine high- and low-flow regions of the conventional outflow pathways. The trabecular meshwork (TM) was occluded using cyanoacrylate glue, except for residual 5-mm TM areas that were either high or low flow at baseline, designating these eyes as "residual high-flow" or "residual low-flow" eyes. Subsequently, outflow was quantitatively reassessed and compared between residual high-flow and residual low-flow eyes followed by indocyanine green angiography. Results: Fluorescein aqueous angiography demonstrated high-flow and low-flow regions. Baseline outflow facilities were 0.320 ± 0.08 and 0.328 ± 0.10 µL/min/mmHg (P = 0.676) in residual high-flow and residual low-flow eyes before TM occlusion, respectively. After partial trabecular meshwork occlusion, outflow facility decreased to 0.209 ± 0.07 µL/min/mmHg (-32.66% ± 19.53%) and 0.114 ± 0.08 µL/min/mmHg (-66.57% ± 23.08%) in residual high- and low-flow eyes (P = 0.035), respectively. There was a significant difference in the resulting IOP increase (P = 0.034). Conclusions: Angiographically determined high- and low-flow regions in the conventional outflow pathways differ in their segmental outflow facility; thus, there is an uneven distribution of local outflow facility across different parts of the TM.

Visual outcomes in carotid stenosis patients treated using endarterectomy.

IntroductionCarotid arthrosclerosis can be a cause of visual impairment. It has been observed that carotid endarterectomy has a positive effect on ophthalmic parameters. The aim of this study was to evaluate the impact of endarterectomy on the optic nerve function.Materials and methods54 asymptomatic patients (19 women and 35 men - 108 eyes) with unilateral carotid stenosis >70% of internal carotid artery, were recruited to the study. All of them were qualified for the endarterectomy procedure. The whole study group underwent Doppler ultrasonography of internal carotid arteries and ophthalmic examination before the surgery, with 22 of them (11 women and 11 men) were examined after the endarterectomy. The ophthalmic examination included; distant best-corrected visual acuity, measurement of the intraocular pressure, electrophysiology (pattern visual evoked potentials), perimetry, and optical coherent tomography (the retinal nerve fiber layer thickness).DiscussionCarotid arteries supply brain and face with blood. Extensive research has observed a concomitant improvement in eyesight after enduring carotid endarterectomy in patients with artery stenosis. This effect was associated with a better blood flow in the ophthalmic artery and its branches, the central retinal artery and the ciliary artery; the major blood supply of the eye.ResultsThe present study proved that carotid endarterectomy has a positive impact on the function of the optic nerve. The visual field parameters and amplitude of pattern visual evoked potentials significantly improved. Preoperative and postoperative values of intraocular pressure and the retinal nerve fiber layer thickness remained stable.

Severe Orbital Congestion After a Brow Lift Due to an Osteodural Arteriovenous Fistula.

The authors describe a 73-year-old woman who developed worsening proptosis, binocular diplopia, and periorbital pain shortly after undergoing an open subperiosteal brow lift procedure. She was found to have a pre-existing osteodural fistula (ODF) within left frontal bone, which was draining through supraorbital vein (SOV) in cavernous sinus. When SOV was inadvertently severed during a brow lift, blood from the fistula was now redirected in the orbit. This is the first report of a decompensated ODF after a brow lift procedure. It underscores the complexity of orbital venous drainage and the importance in preserving the supraorbital and supratrochlear veins during brow lift.

Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma.

The purpose of this study was to ascertain whether a correlation exists between glaucoma-associated alteration of ocular vascular haemodynamics and endothelin-1 (ET-1) levels exist. Eyes of patients with cataract (n = 30) or glaucoma (n = 68) were examined with optical coherence tomography (OCT) and OCT-angiography (OCT-A; AngioVue™-RTVue-XR; Optovue, Fremont, California, USA). The peripapillary and the macular vessel density (VD) values were measured. Inferior and superior retinal nerve fibre layer (RNFL) thickness loss was used for further OCT staging. Aqueous humour of the examined eye and plasma were sampled during cataract or glaucoma surgery and analysed by means of ELISA to determine their ET-1 level. Glaucoma eyes are characterised by reductions in RNFL thickness and VD that correlate significantly with the OCT GSS score. Peripheral and ocular ET-1 level were significantly elevated in patients with glaucoma and correlate positively with the OCT-GSS score of the entire study population. Peripapillary and macula VD of glaucoma patients correlates negatively with plasma ET-1 levels. Multivariable analysis showed a subordinate role of intraocular pressure predictive factor for impaired retinal blood flow compared with plasma ET-1 level in glaucoma. Peripheral ET-1 level serves as risk factor for detection of ocular blood flow changes in the optic nerve head region of glaucomatous eyes.