Retinal Artery Research Articles

Phenotyping vestibulocochlear manifestations in Susac syndrome: a cohort study.

To characterize vestibulocochlear involvement in patients with Susac syndrome (SuS), a rare immune-mediated endotheliopathy of cerebral, retinal and inner ear microvasculature causing a triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. The electronic patient files of 21 patients with SuS are reviewed for data on demography, clinical presentation, disease course and audiovestibular testing. All 21 patients experienced some form of audiovestibular complaints during the disease course, with vertigo and instability being most frequently reported, followed by hearing loss, tinnitus and aural fullness. These audiovestibular symptoms did not always coincide. Fifteen patients had objectified predominant low- to midfrequency sensorineural hearing loss and 8 out of 18 patients showed abnormalities on vestibular testing, most frequently vestibular evoked myogenic potential-abnormalities, indicating otolith dysfunction. Treatment protocols consisted of uniformly extensive immunosuppressive therapy and hearing loss remained mostly mild. Audiovestibular involvement is very common in patients with SuS. Characteristic findings include a "reverse-slope" configuration on audiological testing and otolith dysfunction on vestibular testing. Aggressive immunosuppression may prevent severe audiovestibular dysfunction. Symptoms as aural fullness and otolith dysfunction may indicate an underlying hydrops. Further investigations are necessary to elucidate the histopathological mechanisms underlying these preferentially involved cochleovestibular areas. Early recognition and treatment of SuS are important to stabilize or decrease disease activity and might also have beneficial effects on inner ear outcome. THE SUBMITTED MANUSCRIPT REPORTS DATA DERIVED FROM CLINICAL OBSERVATIONS IN HUMANS: Consent for the research was provided by the Ethics Committee of Ghent University hospital (application number 2019/1443, registration date 31/12/2021, principal investigator Guy Laureys).

Ocular Ultrasound, a neglected tool in the diagnosis of central retinal artery occlusion.

Purpose: To discuss the practical utility of ocular ultrasound in central retinal artery occlusion (CRAO). Methods: Ocular ultrasound was obtained in 4 patients with CRAO using a 20 MHz Annular Array Probe of the ABSolu (Quantel Medical, Texas, USA) ultrasound machine. Results: The causative embolus occluding the central retinal artery was detected on ocular ultrasound imaging in four patients with CRAO. Conclusion: Ocular ultrasound, including newer generation, higher frequency ultrasound probes, aids in the detection of the “retrobulbar spot sign”, a finding that seems to be related to embolic central retinal artery occlusion. This sign will orient investigations towards finding an embolic source.

Brain MRI Should Be Routinely Ordered in Patients Presenting With Acute Retinal Artery Ischemia

Brain MRI Should Be Routinely Ordered in Patients Presenting With Acute Retinal Artery Ischemia

Outcomes of Hyperbaric Oxygen Treatment for Central Retinal Artery Occlusion: A Single Center Experience

PurposeTo describe the outcomes of hyperbaric oxygen therapy (HBOT) for patients with central retinal artery occlusion (CRAO) at a single tertiary care center. DesignRetrospective clinical cohort study. MethodsMedical records of all patients diagnosed with CRAO who received HBOT at Mayo Clinic in Rochester, Minnesota from 1/1/2009 to 12/31/2020 were reviewed to confirm diagnosis, time from onset to presentation, exam findings, treatments, and follow-up data. Main outcome measures included final visual acuity (VA) and number of lines of improvement. ResultsThere were 41 patients diagnosed with CRAO who received HBOT during the 12 year study period. Median time from symptom onset to HBOT treatment was 9.5 hours (interquartile range [IQR] 6.5, 14.0 hours), and patients received a median of 4 HBOT sessions (IQR 2.5, 6.0 sessions). There were 20 patients who received HBOT within 9 hours, 14 (70%) of which had clinically meaningful improvement in VA of ≥0.3 logMAR. In comparison, of the 21 patients treated after 9 hours, 6 (28.6%) had VA improvement of ≥0.3 logMAR (p=0.008). For all patients, the median logMAR VA at presentation was 2.00 (IQR 1.70, 2.30) and the median logMAR VA at follow-up was 1.94 (IQR 1.00, 2.00) (p<0.001), with median lines of improvement of 3.0 (IQR 0.0, 7.0). For patients treated within 9 hours, the median logMAR VA at presentation was 2.00 (IQR 1.93, 2.30) and the median logMAR VA at follow-up was 1.70 (IQR 0.54, 2.00). Patients treated within 9 hours had statistically significant greater median lines of VA improvement than cases that were treated after >9 hours from symptom onset at 5.9 (IQR 3.0, 10.0) and 0.0 (IQR 0.0, 3.0), respectively (p<0.001). There was no difference in VA recovery associated with specific retinal exam findings such as cherry-red spot (p=0.22) and cilioretinal artery perfusion (p=0.36) compared to patients without those findings. ConclusionThere was a statistically significant improvement in VA after HBOT treatment in CRAO patients among patients that received early HBOT, with patients receiving the most benefit when receiving treatment within 9 hours. Randomized control trials in patients with CRAO are required to confirm the efficacy of HBOT.

RETINAL ARTERIAL MACROANEURYSM COMBINED WITH BRANCH RETINAL ARTERY OCCLUSION: Literature Review.

To summarize the causes of retinal arterial microaneurysm combined with branch retinal artery occlusion. The case reports of retinal arterial microaneurysm combined with branch retinal artery occlusion were searched in PubMed, Web of Science, and CNKI databases before May 1, 2024. A total of nine participants from nine case reports were included to analyze factors leading to complications. The reasons for this complication are as follows: complications during photocoagulation therapy. Intraretinal hemorrhage and exudation result in compression of adjacent or distal arteries, resulting in branch retinal artery occlusion. Embolus dislodgement or intraarterial embolus formation can block the artery, damage the wall, and provide conditions for the development of retinal arterial microaneurysm. In addition, it is necessary to be alert to the optic disk macroaneurysm, if hemorrhage or embolus formation in the macroaneurysm will affect the blood supply of the downstream artery, affecting a large range of the retina. Based on the review of case reports, we found that retinal arterial microaneurysm and branch retinal artery occlusion can cause each other. Acute vision loss can result when a complication occurs. In addition, retinal vascular diseases can reflect the whole body, suggesting that ophthalmologists need to pay attention not only to the patient's fundus but also to the patient's systemic diseases.

Moyamoya Disease Increased the Risk of Retinal Vascular Occlusion: A Nationwide Cohort Study in Korea

PurposeTo investigate the risk of retinal vascular occlusion in patients with Moyamoya disease (MMD). DesignRetrospective, longitudinal cohort study using the Korean National Health Insurance Service database. ParticipantsNewly diagnosed MMD patients (n=34,627), who were diagnosed between 2004 and 2022, and their propensity score matched controls (n=136,945) were included. MethodsWe identified retinal vascular occlusion events using diagnostic codes for central retinal artery occlusion, other retinal artery occlusion, and retinal vein occlusion. After a washout-period from 2002 to 2003, information on the diagnosis of retinal vascular occlusion was extracted in both MMD and control group during the follow up period. The association between MMD and the risk of subsequent retinal vascular occlusion was investigated using a time-dependent Cox proportional hazard model and Kaplan-Meier survival analysis with log-rank test adjusted for age, sex, and comorbidities. Main Outcome MeasuresHazard ratios (HRs) and 95% confidence intervals (CIs) for retinal vascular occlusion development according to the MMD. ResultsMMD was associated with an increased risk of subsequent retinal vascular occlusion even after adjusting for confounding variables (HR, 1.22; 95% CI, 1.09–1.36). Among the subtypes of retinal vascular occlusion, central retinal artery occlusion showed a highest HR (2.23; 95% CI, 1.35-3.7). Incidence probability of retinal vascular occlusion was significantly higher among MMD patients than controls (P < 0.001, log-rank test). ConclusionIn this nationwide population-based cohort study, patients with MMD in Korea had an elevated risk of retinal vascular occlusion, suggesting that the MMD is one of the risk factors for retinal vascular occlusion.

Improvement of Visual Hallucinations With Donepezil in Charles Bonnet Syndrome Secondary to Vascular Pathology

ABSTRACTThere is a lack of high‐quality evidence for pharmacological treatment options for Charles Bonnet syndrome and guidelines do not recommend any particular pharmacological option. Here, a case is presented of an older age male who developed complex visual hallucinations following stroke and central retinal artery occlusion (one after the other leading to loss of vision in both eyes), thus indicative of CBS secondary to vascular pathology. This case demonstrates a sustained progressive improvement in hallucinations in CBS following the initiation of acetylcholinesterase inhibitor, donepezil.

Hyperbaric Oxygen Therapy: An Evidence-Based Primer for Emergency Physicians

BackgroundHyperbaric medicine is a subspecialty that many emergency physicians may not encounter frequently in their daily practice. As such, we hope to provide a review, where we present an overview of hyperbaric oxygen therapy, complications from the therapy, and a description of how the treatments are administered. We also discuss seven emergency indications that may benefit from transfer to a hyperbaric facility for treatment. Objective of the ReviewOur aim is to provide an overview of hyperbaric oxygen therapy as it pertains to an emergency physician. We hope that this review will help emergency physicians identify conditions that may benefit from transfer to a hyperbaric facility. DiscussionWe discuss seven emergency conditions that may benefit from transfer to a hyperbaric facility for management – decompression sickness, arterial gas embolism, central retinal artery occlusion, carbon monoxide poisoning, crush injury, necrotizing soft tissue infection, and symptomatic anemia. We also describe special considerations for how to transfer patients needing evaluation by a hyperbaric physician. ConclusionsThis review aims to describe hyperbaric oxygen therapy, identify conditions that may benefit from treatment with hyperbaric oxygen, and discuss management of patients with those conditions as it pertains to an emergency physician.

Multimodal Imaging Characteristics and Correlation to Outcomes in Patients with CRAO Presenting to a Large Academic Center

PurposeTo characterize a large modern cohort of patients with central retinal artery occlusion (CRAO) by describing presenting features and outcomes relating to manually segmented optical coherence tomography (OCT) features, angiographic reperfusion, and visual recovery. DesignRetrospective clinical cohort study. MethodsPatients with CRAO (ICD-10: H34.1) initially presenting to a tertiary referral center between January 2017 and December 2021 were included. Demographics, eye exam findings, fundus photographs, OCT, and fluorescein angiography (FA) were analyzed. Main outcome measures included total and inner retinal thickness on macular OCT, reperfusion, visual outcomes, and development of neovascularization. Results145 eyes of 144 patients with mean age at of 69.4±13.6 years were included. The mean time to presentation was 1.6±4.2 days, with 19% examined within 4.5 hours and 26% within 6 hours of vision loss. 19% had cilioretinal artery (CLRA) sparing. Mean initial visual acuity (VA) was 1.68±1.10 LogMAR (CLRA sparing) compared to 2.53±0.58 LogMAR (non-CLRA sparing), P<0.001. 32% had elevated inflammatory makers. Out of 47 eyes with final fluorescein angiography, one-third showed some reperfusion. Final vision was 1.40±1.16 LogMAR (CLRA sparing) compared to 2.46±0.81 (non-CLRA sparing), P<0.001. A third of patients improved in VA in both groups, 27% of patients gained more than 2 lines of vision in the CLRA sparing group and 36% in the non-CLRA sparing group. 17% improved to better than 20/200 in CLRA-sparing and 4% in non-CLRA sparing. 11% developed neovascularization all in non-CLRA sparing. In a multiple linear regression, VA at presentation was associated with regaining vision of 2 lines or more (OR=2.603, P=0.007). OCT showed progressive thinning over time, reaching lowest measurements at 6 months, and stabilizing thereafter. ConclusionsIn this modern cohort of acute CRAO patients, presentation to a tertiary facility within 12 hours of symptoms was seen in almost half of the patients. Final visual acuity improved in almost a third of the patients, however, vision better than the legal blindness limit was rare (∼5%). Interestingly, a third of patients had some mild elevation of systemic inflammatory markers. Better visual acuity at presentation was associated with visual gain, while baseline OCT values had poor correlation with final outcome.

RFMiD: Retinal Image Analysis for multi-Disease Detection challenge

In the last decades, many publicly available large fundus image datasets have been collected for diabetic retinopathy, glaucoma, and age-related macular degeneration, and a few other frequent pathologies. These publicly available datasets were used to develop a computer-aided disease diagnosis system by training deep learning models to detect these frequent pathologies. One challenge limiting the adoption of a such system by the ophthalmologist is, computer-aided disease diagnosis system ignores sight-threatening rare pathologies such as central retinal artery occlusion or anterior ischemic optic neuropathy and others that ophthalmologists currently detect. Aiming to advance the state-of-the-art in automatic ocular disease classification of frequent diseases along with the rare pathologies, a grand challenge on “Retinal Image Analysis for multi-Disease Detection” was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2021). This paper, reports the challenge organization, dataset, top-performing participants solutions, evaluation measures, and results based on a new “Retinal Fundus Multi-disease Image Dataset” (RFMiD). There were two principal sub-challenges: disease screening (i.e. presence versus absence of pathology — a binary classification problem) and disease/pathology classification (a 28-class multi-label classification problem). It received a positive response from the scientific community with 74 submissions by individuals/teams that effectively entered in this challenge. The top-performing methodologies utilized a blend of data-preprocessing, data augmentation, pre-trained model, and model ensembling. This multi-disease (frequent and rare pathologies) detection will enable the development of generalizable models for screening the retina, unlike the previous efforts that focused on the detection of specific diseases.

Ocular and adnexal manifestations post dengue hemorrhagic fever.

This study aims to present a case series detailing sight-threatening ocular and adnexal manifestations following dengue fever. A retrospective observational study was conducted, analyzing records of patients presenting with ocular manifestations post dengue fever at a tertiary eye care institute in Uttar Pradesh from October 2023 to November 2023. Demographic details, systemic comorbidities, and detailed ophthalmic examinations were recorded. Fifteen eyes of 13 patients with dengue fever were studied. The mean age of presentation was 39.07 years, with a male predominance (84.61%). Systemic comorbidities were noted in 30.76% (diabetes mellitus) and 23.07% (hypertension) of patients. Thrombocytopenia was observed in 53.84% of patients, while 23.07% required blood transfusions, and 15.38% experienced systemic bleeding episodes. The majority of cases were unilateral (84.61%), with the best-corrected visual acuity of perception of light in 84.61% of cases. Diminution of vision was the most common presenting symptom (84.61%), followed by pain (53.84%), redness (38.46%), and watering (23.07%). Major ocular manifestations included panophthalmitis (26.07%), total ophthalmoplegia (26.07%), endogenous endophthalmitis (20%), central retinal artery occlusion (20%), retinal hemorrhage (20%), ischemic optic neuropathy (20%), orbital cellulitis (13.3%), proptosis (13.3%), retrobulbar hemorrhage (13.3%), retinal detachment (13.3%), and foveolitis (6.7%). The diverse array of ocular and adnexal manifestations in dengue hemorrhagic fever may result in permanent visual loss, emphasizing the need for adequate treatment and timely intervention. The risk of sight-threatening complications underscores the importance of early screening by ophthalmologists and increased public awareness.

Automated Detection of Central Retinal Artery Occlusion Using OCT Imaging via Explainable Deep Learning

ObjectiveTo demonstrate the capability of a deep learning model to detect central retinal artery occlusion (CRAO), a retinal pathology with significant clinical urgency, using optical coherence tomography (OCT) data. DesignRetrospective, external validation study analyzing OCT and clinical baseline data of two institutions via deep learning classification analysis. SubjectsPatients presenting to the University Medical Center Tübingen and the University Medical Center Hamburg-Eppendorf in Germany. MethodsOCT-data of patients suffering from CRAO, differential diagnosis with (sub-)acute visual loss (central retinal vein occlusion, diabetic macular edema, non-arteritic ischemic optic neuropathy) and from controls were expertly graded and distinguished into the three groups.Our methodological approach involved a nested multiclass 5-fold cross-validation classification scheme. Main Outcome MeasuresArea under the curve (AUC) ResultsThe optimal performance of our algorithm was observed using 30 epochs, complemented by an early stopping mechanism to prevent overfitting. Our model followed a multiclass approach, distinguishing among the three different classes: Control CRAO and differential diagnoses. The evaluation was conducted by the “one vs. all” area under the receiver operating characteristics (ROC) curve (AUC) method. The results demonstrated AUC of 0.96 (95% confidence interval (CI): ± 0.01), 0.99 (95% CI: ± 0.00), 0.90 (95% CI: ± 0.03) for each class, respectively. ConclusionsOur machine learning algorithm (MLA) exhibited a high AUC, as well as sensitivity and specificity in detecting CRAO and the differential classes, respectively. These findings underscore the potential for deploying MLAs in the identification of less common etiologies within an acute emergency clinical setting.

Cover Image

The cover image is based on the Article Imaging Hypoxia to Predict Primary Neuronal Cell Damage in Branch Retinal Artery Occlusion by Sara Z. Jamal et al., https://doi.org/10.1111/micc.12883. Created in BioRender. Uddin, M. (2023) BioRender.com/p53i167. image

Diagnosis of branch retinal artery occlusion with point-of-care ultrasound

Diagnosis of branch retinal artery occlusion with point-of-care ultrasound

RWC Update: Gas Versus Silicone Oil in the Surgical Management of Proliferative Diabetic Retinopathy; Intraocular Foreign Body with Secondary Branch Retinal Artery Occlusion

RWC Update: Gas Versus Silicone Oil in the Surgical Management of Proliferative Diabetic Retinopathy; Intraocular Foreign Body with Secondary Branch Retinal Artery Occlusion

The association between triglyceride-glucose atherogenic predictor index and central retinal artery occlusion

Purpose: Central retinal artery occlusion (CRAO) is an acute ischemic event causing severe visual loss and is a precursor to further cerebrovascular and cardiovascular events. The triglyceride-glucose index (TyG) indicates insulin resistance in healthy individuals. Numerous research links the TyG index to metabolic syndrome, hypertension, and new-onset diabetes. Recent research also suggests its role as a sign of atherosclerosis in cardiovascular diseases, with potential clinical significance in assessing vascular damage. In this study, the relationship between CRAO and TyG index was evaluated. Materials and Methods: This case-control study involved 116 adults (50 CRAO patients and 66 control subjects without chronic eye diseases) at our hospital from January 2018 to March 2023. The TyG index was formulated as ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2]. Results: The CRAO group had a mean age of 65.0±14.7 years, with 27 (55.1 % 54) females. The control group had a mean age of 61.2±12.1 years, with 32 (48.5) females. The mean TyG index was 9.05±0.7 in the CRAO group and 8.7±0.7 in controls, a statistically significant difference. Univariate regression analysis showed an association between the TyG index and CRAO (OR=2.04; CI: 1.11-3.73). This association remained significant in multivariate logistic regression analysis (OR=1.88; CI: 1.01-3.50). Conclusion: This study found a significantly higher mean TyG index, an atherogenic indicator, in CRAO patients compared to controls.

Relation between peripheral blood inflammatory indices and severity of central retinal artery occlusion.

Central retinal artery occlusion (CRAO) has been identified as an acute emergency resulting in vision loss, with its pathogenesis potentially involving systemic inflammation and abnormal lipid metabolism. Over recent years, it has been established that peripheral blood inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), the systemic immunoinflammatory index (SII), and the monocyte-to-high-density lipoprotein ratio (MHR), play significant roles in assessing systemic inflammation and lipid metabolism. However, the role of these indices in assessing the severity of CRAO has rarely been explored. This study aimd to investigate the relationship between these inflammatory indices and the severity of CRAO. This was a retrospective clinical study with a total of 49 CRAO patients and 50 age- and sex-matched controls involved. The patients with CRAO were divided into three groups (13 with incomplete CRAO, 16 with subtotal CRAO and 20 with total CRAO). Data were compared across these groups, and additionally, correlation analysis, restricted cubic spline plots, and receiver operating characteristic curve analysis were performed. The values of NLR, SII and MHR were significantly higher in the CRAO group compared to controls (NLR: 2.49(1.71,3.44) vs 1.60(1.24,1.97), P<0.001; SII: 606.46(410.25,864.35) vs 403.91(332.90,524.31), P=0.001; MHR: 0.33(0.26,0.44) vs 0.25(0.21,0.34), P<0.001). MHR was also significantly higher in total CRAO than in incomplete CRAO and subtotal CRAO (0.41(0.32,0.60) vs 0.29(0.21,0.43), P=0.036; 0.41(0.32,0.60) vs 0.29(0.23,0.38), P=0.017). Significant positive associations were found between MHR, NLR, SII and both the incidence (all P<0.001) and severity (P<0.001, P<0.001, P=0.003, respectively) of CRAO. MHR had a linear relationship with both the occurrence and severity of CRAO (P-overall=0.013, P-non-linear=0.427 and P-overall=0.013, P-non-linear=0.825). Combining MHR and NLR significantly improved diagnostic efficacy for CRAO and total CRAO, with area under the curve of 0.816 and 0.827, respectively, compared to using MHR alone (0.705 and 0.816). Elevated levels of peripheral blood NLR, SII, and MHR are positively associated with CRAO incidence, highlighting their potential as early predictive markers. The combined NLR and MHR index further enhances diagnostic accuracy and may facilitate timely assessment of CRAO severity by ophthalmologists and internists.

Hemodynamic profiles in idiopathic intracranial hypertension: Doppler ultrasonography as a diagnostic tool for pulsatile tinnitus

Purpose: This study aims to evaluate the role of ophthalmic Doppler ultrasonography (USG) in differentiating IIH patients with and without bilateral PT by analyzing hemodynamic changes in the orbital vessels. Materials and Methods: A prospective, single-center, case-control study was conducted at Harran University from November 2023 to June 2024. The study included 20 IIH patients. Participants underwent clinical assessments, ophthalmic evaluations, brain imaging, lumbar puncture, and transorbital sonography. IIH patients were categorized into PT (n=8) and non-PT (n=12) groups. Doppler USG measured end-diastolic velocity (EDV), peak systolic velocity (PSV), time-averaged velocity (TAV), resistive index (RI), pulsatility index (PI), and systolic to the diastolic ratio (S/D) of the central retinal artery. Results: Significant differences were observed in left eye EDV and TAV, with lower values in the PT group. Although not statistically significant, right-eye EDV and TAV also trended lower in the PT group. Additionally, both eyes' PSV values showed a trend toward statistical significance, being lower in the PT group. ROC curve analysis identified optimal thresholds for left eye EDV (5.35; sensitivity 75%, specificity 83.33%) and TAV (9; sensitivity 50%, specificity 91.67%). Conclusion: Orbital Doppler USG reveals distinct hemodynamic profiles in IIH patients with PT, suggesting EDV and TAV as potential biomarkers. Larger cohort studies are needed to validate and clarify IIH-PT mechanisms.

Central Retinal Artery Occlusion Following Intralesional Triamcinolone Injection for IgG4-related Orbital Disease.

The risk of blindness associated with periocular and facial injections is well documented. Previous cases describing vision loss following a recent periocular or facial injection have emphasized the importance of facial "danger zones." To date, the literature suggests that nearly half of all cases of central retinal artery occlusion in the setting of a recent periocular or facial injection involve an injection in or around the nose. Here, the authors report the second known case of central retinal artery occlusion following a triamcinolone injection to the lacrimal gland. A 30-year-old female with a diagnosis of IgG4-related disease underwent lacrimal gland debulking with an intralesional steroid injection. She noted OD vision loss immediately after surgery, with posterior segment examination demonstrating retinal whitening with a cherry-red spot and intra-arterial yellow-white plaques. This case serves as a reminder to clinicians regarding the risk of iatrogenic embolism following triamcinolone injections around the face with special attention drawn to the lacrimal gland.

Vascular changes in the retinal capillary network in fellow eye of the patients with central retinal artery occlusion.

We aimed to evaluate the retinal vascular changes in the superficial and deep retinal vascular networks in the fellow eye of patients with central retinal artery occlusion (CRAO) and compare them with controls using optical coherence tomography angiography (OCT-A). In a cross-sectional study, 27 patients with CRAO and 189 normal controls were included. Ophthalmic examination and OCT-A images were performed on all participants. The total vascular density of the superficial capillary network in the 6-mm scan was significantly lower in the fellow eye of patients with CRAO than in the control group (p = 0.02). No significant difference was observed in the FAZ area of the affected eyes and their fellow eyes compared with the controls. Total vascular density at 300 microns around the fovea was lower in the fellow eye compared with the control group (p = 0.034). The retinal vascular network changes in the fellow eyes of patients with CRAO suggest that persistent microvascular changes may be present before the onset of CRAO. This finding indicates that such changes could serve as an early diagnostic window for systemic vascular changes before catastrophic vascular events occur.