Alzheimer's disease pathophysiology in the Retina.

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid ß-protein (Aß) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aß deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

A Comparative Study of Large Language Models, Human Experts, and Expert-Edited Large Language Models to Neuro-Ophthalmology Questions.

BACKGROUND: While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology. METHODS: This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023. We randomly assigned 21 neuro-ophthalmology questions to 13 experts. Each expert provided an answer and then edited a ChatGPT-4-generated response, timing both tasks. In addition, 5 LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, Bard) generated responses. Anonymized and randomized responses from Expert + AI, human experts, and LLMs were evaluated by the remaining 12 experts. The main outcome was the mean score for quality and empathy, rated on a 1-5 scale. RESULTS: Significant differences existed between response types for both quality and empathy (P < 0.0001, P < 0.0001). For quality, Expert + AI (4.16 ± 0.81) performed the best, followed by GPT-4 (4.04 ± 0.92), GPT-3.5 (3.99 ± 0.87), Claude (3.6 ± 1.09), Expert (3.56 ± 1.01), Bard (3.5 ± 1.15), and Bing (3.04 ± 1.12). For empathy, Expert + AI (3.63 ± 0.87) had the highest score, followed by GPT-4 (3.6 ± 0.88), Bard (3.54 ± 0.89), GPT-3.5 (3.5 ± 0.83), Bing (3.27 ± 1.03), Expert (3.26 ± 1.08), and Claude (3.11 ± 0.78). For quality (P < 0.0001) and empathy (P = 0.002), Expert + AI performed better than Expert. Time taken for expert-created and expert-edited LLM responses was similar (P = 0.75). CONCLUSIONS: Expert-edited LLM responses had the highest expert-determined ratings of quality and empathy warranting further exploration of their potential benefits in clinical settings.

Thrombolytic Therapy for Central Retinal Artery Occlusion in an Academic Multi-Site Stroke Centre.

Central retinal artery occlusion (CRAO) is a subtype of acute ischaemic stroke leading to severe visual loss. A recent American Heart Association scientific statement proposed time-windows for thrombolysis in CRAO similar to acute ischaemic cerebral strokes. We aimed to review our academic multi-site stroke centre experience with intravenous (IVT) and intra-arterial thrombolysis (IAT) in CRAO between 1997 and 2022. Demographic, clinical characteristics, thrombolysis timeline, concurrent therapies, complications, and 3-month follow-up visual acuity (VA) were collected. The thrombolysed cohort follow-up VA was compared with an age, gender and baseline VA matched cohort of CRAO patients that received conservative therapies. Thrombolytic therapy was administered to 3.55% (n = 20) of CRAO admissions; 13 IVT (mean age 68, 61.5% male, 12 alteplase and 1 tenecteplase, all embolic aetiology, 1 CRAO mimic) and 7 IAT (mean age 55, 85.7% male, 3 post-operative and 3 embolic). Additional conservative CRAO-targeting therapies was received by 60%. The median time from onset of visual loss to IVT was 158 minutes (range 67-260). Improvement by at least two Snellen lines was achieved by 25% with 12.5% improving to 20/100 or better. Intracranial haemorrhage post IVT occurred in 1/13 (7.6%). The median time from onset of visual loss to IAT was 335 minutes. Improvement by at least two Snellen lines was achieved by 42%. No difference in 3-month VA was noted between patients that received thrombolysis, either alone (n = 8) or combined with other therapies, and those that received conservative therapies. Our results suggest that the management of acute CRAO remains heterogeneous. The lack of obvious benefit of thrombolysis in our small series supports the need for randomizsd clinical trials comparing thrombolysis to placebo to guide hyperacute CRAO management.

Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance.

Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures. Results: Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count. Discussion: Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD. Highlights: Retinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions.Secondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes.Cognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes.

Thrombolysis for central retinal artery occlusion: An individual participant-level meta-analysis.

BACKGROUND: Whether thrombolysis improves outcomes in non-arteritic central retinal artery occlusion (naCRAO) is uncertain. We aimed to evaluate the rate of visual recovery after intra-venous thrombolysis (IVT) or intra-arterial thrombolysis (IAT) administration of tissue plasminogen activator (tPA) or urokinase among patients with naCRAO and explore the parameters affecting the final visual acuity (VA). AIM: We systematically searched six databases. Logarithm of the minimum angle of resolution (logMAR) and VA of ⩾20/100 were used to quantify visual recovery. To explore the role of other factors on visual recovery, we defined two models for studies with aggregated data (designs 1 and 2) and 16 models for individual participant data (IPD, models 1-16). SUMMARY OF REVIEW: We included data from 771 patients out of 72 publications in nine languages. Visual improvement for ⩾0.3 logMAR was reported in 74.3% of patients who received IVT-tPA within 4.5 h (CI: 60.9-86.0%; unadjusted rate: 73.2%) and 60.0% of those who received IAT-tPA within 24 h (CI: 49.1-70.5%; unadjusted rate: 59.6%). VA of ⩾20/100 was observed among 39.0% of patients after IVT-tPA within 4.5 h and 21.9% of those with IAT-tPA within 24 h. IPD models highlighted the association between improved visual outcomes and VA at presentation, at least 2 weeks follow-up before reporting the final VA, antiplatelet therapy, and shorter symptom onset to thrombolysis window. CONCLUSION: Early thrombolytic therapy with tPA is associated with enhanced visual recovery in naCRAO. Future studies should refine the optimum time window for thrombolysis in naCRAO.

Pitfalls and biases in neuroepidemiological studies of COVID-19 and the nervous system: a critical appraisal of the current evidence and future directions.

BACKGROUND: Neurological manifestations frequently occur in individuals with COVID-19, manifesting during the acute phase, persisting beyond the resolution of acute symptoms, and appearing days or weeks after the initial onset of COVID-19 symptoms. However, predicting the incidence, course, and outcome of these neurological manifestations at the individual patient level remains challenging. Biases in study design and limitations in data collection may contribute to the inconsistency and limited validity of the reported findings. Herein, we focused on critically appraising pitfalls and biases of prior reports and provide guidance for improving the quality and standardization of future research. Patients with COVID-19 exhibit diverse demographic features, sociocultural backgrounds, lifestyle habits, and comorbidities, all of which can influence the severity and progression of the infection and its impact on other organ systems. Overlooked or undocumented comorbidities and related treatments may contribute to neurological sequelae, which may not solely be attributable to COVID-19. It is crucial to consider the potential side effects of vaccines in relation to neurological manifestations. CONCLUSION: To investigate neurological manifestations of COVID-19, it is essential to employ valid and reliable diagnostic criteria and standard definitions of the factors of interest. Although population-based studies are lacking, well-defined inception cohorts, including hospitalized individuals, outpatients, and community residents, can serve as valuable compromises. These cohorts should be evaluated for the presence of common comorbidities, alongside documenting the primary non-neurological manifestations of the infectious disease. Lastly, patients with COVID-19 should be followed beyond the acute phase to assess the persistence, duration, and severity of neurological symptoms, signs, or diseases.

OPTIMAL TRANSPORT GUIDED UNSUPERVISED LEARNING FOR ENHANCING LOW-QUALITY RETINAL IMAGES.

Real-world non-mydriatic retinal fundus photography is prone to artifacts, imperfections, and low-quality when certain ocular or systemic co-morbidities exist. Artifacts may result in inaccuracy or ambiguity in clinical diagnoses. In this paper, we proposed a simple but effective end-to-end framework for enhancing poor-quality retinal fundus images. Leveraging the optimal transport theory, we proposed an unpaired image-to-image translation scheme for transporting low-quality images to their high-quality counterparts. We theoretically proved that a Generative Adversarial Networks (GAN) model with a generator and discriminator is sufficient for this task. Furthermore, to mitigate the inconsistency of information between the low-quality images and their enhancements, an information consistency mechanism was proposed to maximally maintain structural consistency (optical discs, blood vessels, lesions) between the source and enhanced domains. Extensive experiments were conducted on the EyeQ dataset to demonstrate the superiority of our proposed method perceptually and quantitatively.

OTRE: Where Optimal Transport Guided Unpaired Image-to-Image Translation Meets Regularization by Enhancing.

Non-mydriatic retinal color fundus photography (CFP) is widely available due to the advantage of not requiring pupillary dilation, however, is prone to poor quality due to operators, systemic imperfections, or patient-related causes. Optimal retinal image quality is mandated for accurate medical diagnoses and automated analyses. Herein, we leveraged the Optimal Transport (OT) theory to propose an unpaired image-to-image translation scheme for mapping low-quality retinal CFPs to high-quality counterparts. Furthermore, to improve the flexibility, robustness, and applicability of our image enhancement pipeline in the clinical practice, we generalized a state-of-the-art model-based image reconstruction method, regularization by denoising, by plugging in priors learned by our OT-guided image-to-image translation network. We named it as regularization by enhancing (RE). We validated the integrated framework, OTRE, on three publicly available retinal image datasets by assessing the quality after enhancement and their performance on various downstream tasks, including diabetic retinopathy grading, vessel segmentation, and diabetic lesion segmentation. The experimental results demonstrated the superiority of our proposed framework over some state-of-the-art unsupervised competitors and a state-of-the-art supervised method.

Telemedicine for Acute Monocular Visual Loss: A Retrospective Large Telestroke Network Experience.

Introduction: Central retinal artery occlusion (CRAO) is an under-recognized stroke subtype that may benefit from hyperacute reperfusion therapies. We aimed to evaluate the ability of telestroke activations to provide CRAO diagnosis and thrombolysis. Methods: This retrospective observational study investigates all encounters conducted for acute visual loss between 2010 and 2021 in our multicentric Mayo Clinic Telestroke Network. Demographics, time from visual loss to telestroke evaluation, ocular examination, diagnostic, and therapeutic recommendations were collected for CRAO subjects. Results: Out of 9,511, 49 encounters (0.51%) were conducted for an acute ocular complaint. Five patients had possible CRAO, and 4 presented within 4.5 h from symptom onset (range 1.5-5 h). None received thrombolytic therapy. All telestroke physicians recommended ophthalmology consultation. Conclusion: Current telestroke assessment of acute visual loss is suboptimal and patients eligible for acute reperfusion therapies may not be offered treatment. Teleophthalmologic evaluations and advanced ophthalmic diagnostic tools should complement telestroke systems.

Unilateral Optic Nerve Diffusion Restriction After Sinus Surgery Secondary to Central Retinal Artery Occlusion: Case Report and Literature Review.

INTRODUCTION: Permanent perioperative vision loss is caused by ischemic optic neuropathy (ION) or central retinal artery occlusion (CRAO). Whereas diffusion restriction of the optic nerve (ON) on brain magnetic resonance imaging has been previously reported in perioperative posterior ION (PION), there are no reports of ON diffusion restriction in patients diagnosed with acute perioperative CRAO. We present a case of perioperative CRAO to highlight this neuroimaging finding for neuroradiologists and neurologists. CASE REPORT: A 71-year-old male without vascular risk factors underwent maxillary bilateral antrostomy and septoplasty for chronic sinusitis. Twenty to thirty minutes upon awakening, he complained of painless left eye vision loss. Ophthalmoscopic examination showed retinal whitening, segmented arterioles, and hyperemic disc. Brain MR-diffusion weighted imaging/apparent diffusion coefficient revealed ON diffusion restriction in the proximal segment. Despite attempted reperfusion, left eye remained with no light perception at 6 months. Patients undergoing nonocular surgeries who develop perioperative vision loss related to PION may exhibit ON diffusion restriction but usually have normal ophthalmoscopic findings. CRAO shows retinal whitening, edema, segmentation of arterioles, and cherry red spot on ophthalmoscopy. A recent study reported that ON diffusion restriction in nonperioperative CRAO cases has a sensitivity and specificity of 55% and 70% to 100%. Here, PION was initially considered based on imaging. However, given the neuro-ophthalmic findings, a proximal embolus in the central retinal artery, obstructing its entrance into the proximal ON was deemed more likely. CONCLUSION: We highlight that proximal ON diffusion restriction on brain magnetic resonance imaging can be diagnostic of proximal thromboembolic CRAO. Future studies should evaluate the diagnostic utility and accuracy of MR-diffusion weighted imaging/apparent diffusion coefficient in perioperative visual loss.

A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study.

BACKGROUND: There is no simple model to screen for Alzheimer's disease, partly because the diagnosis of Alzheimer's disease itself is complex-typically involving expensive and sometimes invasive tests not commonly available outside highly specialised clinical settings. We aimed to develop a deep learning algorithm that could use retinal photographs alone, which is the most common method of non-invasive imaging the retina to detect Alzheimer's disease-dementia. METHODS: In this retrospective, multicentre case-control study, we trained, validated, and tested a deep learning algorithm to detect Alzheimer's disease-dementia from retinal photographs using retrospectively collected data from 11 studies that recruited patients with Alzheimer's disease-dementia and people without disease from different countries. Our main aim was to develop a bilateral model to detect Alzheimer's disease-dementia from retinal photographs alone. We designed and internally validated the bilateral deep learning model using retinal photographs from six studies. We used the EfficientNet-b2 network as the backbone of the model to extract features from the images. Integrated features from four retinal photographs (optic nerve head-centred and macula-centred fields from both eyes) for each individual were used to develop supervised deep learning models and equip the network with unsupervised domain adaptation technique, to address dataset discrepancy between the different studies. We tested the trained model using five other studies, three of which used PET as a biomarker of significant amyloid ß burden (testing the deep learning model between amyloid ß positive vs amyloid ß negative). FINDINGS: 12 949 retinal photographs from 648 patients with Alzheimer's disease and 3240 people without the disease were used to train, validate, and test the deep learning model. In the internal validation dataset, the deep learning model had 83·6% (SD 2·5) accuracy, 93·2% (SD 2·2) sensitivity, 82·0% (SD 3·1) specificity, and an area under the receiver operating characteristic curve (AUROC) of 0·93 (0·01) for detecting Alzheimer's disease-dementia. In the testing datasets, the bilateral deep learning model had accuracies ranging from 79·6% (SD 15·5) to 92·1% (11·4) and AUROCs ranging from 0·73 (SD 0·24) to 0·91 (0·10). In the datasets with data on PET, the model was able to differentiate between participants who were amyloid ß positive and those who were amyloid ß negative: accuracies ranged from 80·6 (SD 13·4%) to 89·3 (13·7%) and AUROC ranged from 0·68 (SD 0·24) to 0·86 (0·16). In subgroup analyses, the discriminative performance of the model was improved in patients with eye disease (accuracy 89·6% [SD 12·5%]) versus those without eye disease (71·7% [11·6%]) and patients with diabetes (81·9% [SD 20·3%]) versus those without the disease (72·4% [11·7%]). INTERPRETATION: A retinal photograph-based deep learning algorithm can detect Alzheimer's disease with good accuracy, showing its potential for screening Alzheimer's disease in a community setting. FUNDING: BrightFocus Foundation.

Improving the Telemedicine Evaluation of Patients With Acute Vision Loss: A Call to Eyes.

Acute vision loss related to cerebral or retinal ischemia is a time-sensitive emergency with potential treatment options including IV or intra-arterial thrombolysis and mechanical thrombectomy. However, patients either present in a delayed fashion or present to an emergency department that lacks the subspecialty expertise to recognize and treat these conditions in a timely fashion. Moreover, health care systems in the United States are becoming increasingly reliant on telestroke and teleneurology services for acute neurologic care, making the accurate diagnosis of acute vision loss even more challenging due to critical limitations to the remote video evaluation, including the inability to perform routine ophthalmoscopy. The COVID-19 pandemic has led to a greater reliance on telemedicine services and helped to accelerate the development of novel tools and care pathways to improve remote ophthalmologic evaluation, but these tools have yet to be adapted for use in the remote evaluation of acute vision loss. Permanent vision loss can be disabling for patients, and efforts must be made to increase and improve early diagnosis and management. Herein, the authors outline the importance of improving acute ophthalmologic diagnosis, outline key limitations and barriers to the current video-based teleneurology assessments, highlight opportunities to leverage new tools to enhance the remote assessment of vision loss, and propose new avenues to improve access to emergent ophthalmology subspecialty.

Embolic Stroke in Setting of Iliac Vein Stenosis in an Avid Cyclist.

External iliac vein stenosis related to cycling has rarely been reported as a cause of deep vein thrombosis. Ischemic stroke occurring in this condition due to paradoxical embolism across a preexisting patent foramen ovale (PFO) has yet to be reported. Here we report a case of embolic ischemic strokes in a young, avid cyclist with no prior known vascular risk factors. A thorough cerebrovascular workup revealed a right-to-left shunt on transesophageal echocardiogram that prompted venous thrombosis evaluation. Pelvic MR venogram demonstrated a 3.5 cm high-grade stenosis of the right external iliac vein, concerning for possible prior thrombotic disease. His strokes were deemed most likely a result of paradoxical emboli originating in the pelvis at the site of right external iliac vein stenosis. The patient ultimately opted for PFO closure for secondary stroke prevention, as he wished to continue daily cycling. This case highlights the importance of neurohospitalists considering iliac vein stenosis as a potential cause of embolic stroke of undetermined source, especially in young patients who are avid cyclists, as part of a thorough vascular workup.

Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks.

ABSTRACT: Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA.All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended.The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.

Self-Supervised Equivariant Regularization Reconciles Multiple Instance Learning: Joint Referable Diabetic Retinopathy Classification and Lesion Segmentation.

Lesion appearance is a crucial clue for medical providers to distinguish referable diabetic retinopathy (rDR) from non-referable DR. Most existing large-scale DR datasets contain only image-level labels rather than pixel-based annotations. This motivates us to develop algorithms to classify rDR and segment lesions via image-level labels. This paper leverages self-supervised equivariant learning and attention-based multi-instance learning (MIL) to tackle this problem. MIL is an effective strategy to differentiate positive and negative instances, helping us discard background regions (negative instances) while localizing lesion regions (positive ones). However, MIL only provides coarse lesion localization and cannot distinguish lesions located across adjacent patches. Conversely, a self-supervised equivariant attention mechanism (SEAM) generates a segmentation-level class activation map (CAM) that can guide patch extraction of lesions more accurately. Our work aims at integrating both methods to improve rDR classification accuracy. We conduct extensive validation experiments on the Eyepacs dataset, achieving an area under the receiver operating characteristic curve (AU ROC) of 0.958, outperforming current state-of-the-art algorithms.

Disparate trends of atherosclerotic plaque evolution in stroke patients under 18-month follow-up: a 3D whole-brain magnetic resonance vessel wall imaging study.

PURPOSE: The trend of atherosclerotic plaque feature evolution is unclear in stroke patients with and without recurrence. We aimed to use three-dimensional whole-brain magnetic resonance vessel wall imaging to quantify the morphological changes of causative lesions during medical therapy in patients with symptomatic intracranial atherosclerotic disease. METHODS: Patients with acute ischemic stroke attributed to intracranial atherosclerotic disease were retrospectively enrolled if they underwent both baseline and follow-up magnetic resonance vessel wall imaging. The morphological features of the causative plaque, including plaque volume, peak normalized wall index, maximum wall thickness, degree of stenosis, pre-contrast plaque-wall contrast ratio, and post-contrast plaque enhancement ratio, were quantified and compared between the non-recurrent and recurrent groups (defined as the recurrence of a vascular event within 18 months of stroke). RESULTS: Twenty-nine patients were included in the final analysis. No significant differences were found in plaque features in the baseline scan between the non-recurrent (n = 22) and recurrent groups (n = 7). The changes in maximum wall thickness (-13.32% vs. 8.93%, P = 0.026), plaque-wall contrast ratio (-0.82% vs. 3.42%, P = 0.005) and plaque enhancement ratio (-11.03% vs. 9.75%, P = 0.019) were significantly different between the non-recurrent and recurrent groups. Univariable logistic regression showed that the increase in plaque-wall contrast ratio (odds ratio 3.22, 95% confidence interval 1.55-9.98, P = 0.003) was related to stroke recurrence. CONCLUSION: Morphological changes of plaque features on magnetic resonance vessel wall imaging demonstrated distinct trends in symptomatic intracranial atherosclerotic disease patients with and without stroke recurrence.

Migrainous infarction of the eye: Two cases of monocular ischemic complications associated with retinal migraine.

BACKGROUND: Retinal migraine is defined by fully reversible monocular visual phenomena. We present two cases that were complicated by permanent monocular vision deficits. CASES: A 57-year-old man with history of retinal migraine experienced persistent monocular vision loss after one stereotypical retinal migraine, progressing to finger-count vision over 4 days. He developed paracentral acute middle maculopathy that progressed to central retinal artery occlusion. A 27-year-old man with history of retinal migraine presented with persistent right eye superotemporal scotoma after a retinal migraine. Relative afferent pupillary defect and superotemporal visual field defect were noted, consistent with ischemic optic neuropathy. CONCLUSION: Retinal migraine can complicate with permanent monocular visual loss, suggesting potential migrainous infarction of the retina or optic nerve. A thorough cerebrovascular evaluation must be completed, which was unrevealing in our cases. Acute and preventive migraine therapy may be considered in retinal migraine patients, to mitigate rare but potentially permanent visual loss.

The Clinical Utility of High-Resolution Vessel Wall Imaging in Screening for Meningovascular Neurosyphilis.

Meningovascular neurosyphilis is a common cause of stroke in young adults, particularly when HIV co-infection is present. Contemporary screening for neurosyphilis relies on invasive testing. High resolution vessel wall imaging (HR-VW) is an emerging non-invasive tool to detect intracranial vessel wall inflammation. We report a case of multifocal acute cerebral infarctions from meningovascular neurosyphillis in which HR-VWI was instrumental in leading to the etiological diagnosis. A 32-year-old man with history of untreated HIV and polysubstance abuse presented with sudden onset vertigo. CT angiogram of the head and neck showed non-dominant left extracranial vertebral artery occlusion in the V1 segment, and multifocal areas of stenoses in V2 through V4 segments. Non-contrast brain MRI demonstrated multiple small acute infarcts in the left cerebellum, left brachium pontis, medulla and occipital lobe. Rapid plasma reagin was reactive. 3D whole-brain HR-VWI revealed concentric vessel wall contrast enhancement in the left V4 segment, suggestive of inflammation. This HR-VWI finding prompted further investigation with cerebrospinal fluid analysis that revealed reactive fluorescent treponemal antibody absorption test. The patient received high-dose intravenous Penicillin G, was restarted on highly active antiretroviral therapy, and remained neurologically stable to-date. With high spatial resolution and signal-to-noise ratio, HR-VWI allows for visualization of vessel wall inflammation in co-morbid HIV and neurosyphilis.

Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study.

INTRODUCTION: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. METHODS: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. RESULTS: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). CONCLUSION: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.