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AIM OF STUDY: To retrospectively assess the occurrence and consequences of subarachnoid haemorrhages (SAH) caused by ruptured intracranial aneurysms (RIA), particularly focusing on the treatment outcomes of small aneurysms treated with either endovascular embolisation or surgical intervention. MATERIAL AND METHODS: We retrospectively analysed data from 408 patients (144 males and 264 females) who were hospitalised between 2013 and 2022 at the Department of Neurosurgery and Neurology in University Hospital Nr 2 in Bydgoszcz, Poland. Clinical conditions at admission, assessed using the Glasgow Coma Scale, Hunt-Hess scale (H-H), modified Rankin scale (mRS), as well as age and sex, were recorded. Additionally, aneurysm data including size, localisation, and the method and outcome of endovascular or surgical treatment were examined. RESULTS: Among the 408 patients hospitalised due to SAH, the most common localisation of the 375 RIAs was the anterior communicating artery (AcomA) complex (111 cases, 29.6%), followed by the medial cerebral artery (MCA) (95 cases, 25.3%), internal carotid artery (ICA) (94 cases, 25%), and the vertebrobasilar complex (consisting of the basilar artery (BA) - 25 cases, vertebral artery (VA) - 13 cases, anterior inferior cerebellar artery (AICA) - one case, and posterior inferior cerebellar artery (PICA) - four cases), which accounted for 43 SAH cases (11.46%). In 33 cases, neither RIA nor a haemorrhage source was identified, or arteriography showed no cerebral arteries contrast flow. Among the examined group of 375 RIAs, 45 (12%) were microaneurysms (≤ 3 mm), 35 (9%) were small aneurysms (3 ≤ 5 mm), 89 (24%) were medium-sized (5 ≤ 7 mm), and 151 (40%) were large aneurysms (> 7 mm), serving as the source of SAH. A better outcome was significantly associated with lower initial H-H grade (p < 0.001), higher GCS (p < 0.001), lower mRS at admission (p < 0.001), younger age (p < 0.001), smaller size (≤ 3 mm) (p < 0.001), and endovascular treatment (p < 0.001). CONCLUSIONS: In this series, over 21% of patients suffered from SAH resulting from ruptured small aneurysms (≤ 5 mm), with 12% specifically attributed to ruptured very small aneurysms (≤ 3 mm), despite large aneurysms (> 7 mm) being the most prevalent source of bleeding in 40% of cases. A worse prognosis was primarily associated with the severity of SAH, reflected in poorer clinical status at admission and older age. Endovascular embolisation was found to be effective and associated with better outcomes compared to surgical treatment.

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Introduction: We report on one case of age-related macular degeneration and one case of diabetic macular edema with concomitant retinal arterial macroaneurysm (RAM) that were treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections. Case Presentation: Case 1 involved a 71-year-old woman with a 30-year history of diabetes who was undergoing dialysis. Pretreatment visual acuity in the right eye was 0.4. Fundus fluorescein angiography (FA) showed that numerous microaneurysms and RAM were located at a distance of two papillary diameters from the macular area. Diabetic macular edema was diagnosed. After 12 anti-VEGF injections, the macular edema resolved, microaneurysms decreased, and the RAM also disappeared. Visual acuity in the right eye improved to 0.7. Case 2 involved an 81-year-old woman receiving treatment for disorders including hypertension and dyslipidemia. Pretreatment visual acuity in the right eye was 0.03. And vitreous hemorrhage was present. After one ranibizumab intravitreal injection, the fundus became clearly visible. Macular subretinal hemorrhage and an RAM in the upper macula area were evident on FA and optical coherence tomography. After four intravitreal injections of ranibizumab, macular hemorrhage resolved, RAM disappeared, and visual acuity improved to 0.2. All cases were treated by intravitreal injection of anti-VEGF. After several injections, the macular hemorrhage or macular edema was resolved. RAM disappeared, and visual acuity improved. Conclusion: Intravitreal injection of anti-VEGF appears effective for age-related macular degeneration or diabetic macular edema with concomitant RAM. Although anti-VEGF intravitreal injections are not covered by health insurance for the treatment of RAM, their effectiveness means that the expansion of indications is desirable.

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A 40-year-old female with a history of ischemic moyamoya disease treated with indirect revascularization at ages 12 and 25 years presented with a sudden severe headache. Imaging studies revealed focal parenchymal hemorrhage and acute subdural hematoma, confirming a microaneurysm formed on the postoperative transosseous vascular network as the source of bleeding. Conservative management was performed, and no hemorrhage recurred during the 6-month follow-up period. Interestingly, follow-up imaging revealed spontaneous occlusion of the microaneurysm. However, due to the rarity of this presentation, the efficacy of conservative treatment remains unclear. Further research on similar cases is warranted.

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Objective: This study aimed to investigate and compare the efficacy and safety of retinal laser photocoagulation (PRP) alone, PRP with aflibercept 3+PRN, and PRP with aflibercept 5+PRN in patients with both high-risk proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Methods: Overall, 170 patients with high-risk PDR and DME (170 eyes from 170 patients) who visited our ophthalmology clinic from December 2018 to December 2020 were divided into the PRP (n=58), aflibercept 5+PRN with PRP (n=53), and aflibercept 3+PRN with PRP (n= 59) groups. General information, such as age, sex, and eye category, was obtained. Moreover, best-corrected visual acuity (BCVA), baseline central macular foveal thickness (CFT), microaneurysm (MA), area of neovascularization (NV), area of hard exudate (HE), and cytokine levels in atrial fluid before and after treatment, were assessed. The χ2 test was used for comparison between groups for statistical data. Analysis of variance was used for the statistical description of measurement data, independent samples were analyzed using Student's t-test, and Student-Newman-Keuls test was used for group comparisons. Differences were considered statistically significant at P < 0.05. Results: After treatment, no significant improvement in the BCVA (logMAR) of patients in the PRP group was observed. The BCVA (log MAR) decreased from 0.72 ± 0.17 and 0.74 ± 0.17 to 0.50 ± 0.13 and 0.53 ± 0.17 in PRP with aflibercept 5+PRN and PRP with aflibercept 3+PRN groups, respectively, with a statistically significant difference compared to those in the PRP group (P<0.05 in all cases). However, no statistically significant difference was observed between the combined treatment groups (P>0.05). The CFT in the PRP-only group decreased slightly from 361.80 ± 36.70 µm to 353.86 ± 40.88 µm, with no statistically significant difference (P>0.05), whereas the CFT in the aflibercept 5+PRN with PRP and aflibercept 3+PRN with PRP groups decreased from 356.57 ± 37.57 µm and 358.17 ± 44.66 µm to 284.87 ± 31.52 µm and 303.19 ± 37.00 µm, respectively, with statistically significant differences before and after treatment (P<0.05 for both groups). Statistically significant differences were observed in CFT between the three groups after treatment (P<0.05 in all cases). The number of MA (pcs) in the PRP, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups decreased from 118.34 ± 27.96, 118.60 ± 33.34, and 116.59 ± 28.95 to 92.95 ± 29.04, 44.60 ± 20.73, and 54.26 ± 25.43, respectively. The two-way comparison of the three groups revealed statistically significant differences in MA (P<0.05 in all cases). In the three groups, NV decreased from 1.00 ± 0.21 mm², 1.01 ± 0.18 mm², and 0.98 ± 0.20 mm² before treatment to 0.49 ± 0.17 mm², 0.31 ± 0.16 mm², and 0.38 ± 0.14 mm², respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, 13, 18, and 18 patients had reduced HE area in the PRP-only, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups, respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, vascular endothelial growth factor, monocyte chemoattractant protein-1, and glial fibrilliary acidic protein levels (pg/mL) in the aqueous humor decreased in both combined treatment groups compared with that at baseline, with statistically significant differences; however, no significant difference was observed between the two combined treatment groups (P>0.05). Conclusion: Aflibercept 5+PRN combined with PRP was safe and effective in treating patients with high-risk PDR and DME, and was more effective than PRP-only and aflibercept 3+PRN with PRP in improving CFT and MA.

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Purpose: To report a case of a refractory foveal microaneurysm (MA) that was successfully treated by use of a new surgical procedure. Observations: This study involved a 79-year-old female with an active foveal MA associated with branch retinal vein occlusion in her left eye. Despite anti-vascular endothelial growth factor treatments, the MA remained active without closure, and best-corrected visual acuity (VA) gradually decreased from 20/20 to 20/200. After our new surgical procedure was explained in detail to the patient, written informed consent was obtained from the patient and the surgery was performed. Briefly, following pars plana vitrectomy, the internal limiting membrane in her left eye was peeled and the retina of the external wall of the MA was then gently incised. The exposed MA was then directly grabbed and pulled up onto the retina using 27-gauge microforceps, and photocoagulation was performed. At 3-months postoperative, closure of the MA and improvement in the retinal findings were observed, and best-corrected VA improved to 20/67. Conclusions and importance: We report a case of a refractory foveal MA that was successfully treated with a novel surgical technique that closed the MA, avoided thermal damage to the surrounding tissue, and resulted in improved postoperative VA.

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Purpose: In this study, we report a patient who presented with both chronic myelocytic leukemia (CML) and Susac syndrome (SS). Observations: A 45-year-old male diagnosed with CML in the blast phase sought consultation due to a deterioration in vision in his right eye. He also had hearing loss and severe migraneous headaches. Best corrected visual acuity was light perception and 20/20 in the right and left eyes, respectively. The slit lamp examination and intraocular pressure were within normal ranges for both eyes. Upon dilated fundoscopy, organized vitreous hemorrhage was observed in the right eye, while the left eye exhibited extensive sclerotic vessels with retinal neovascularization in the periphery. Ultrasound of the right eye showed tractional retinal detachment. Optical coherence tomography of the left retina showed thinning of the retina in temporal macula. Fluorescein angiography revealed a substantial nonperfused region in the peripheral left retina, accompanied by arterioarterial and arteriovenous collaterals, along with microaneurysms. MRI showed scattered foci of hyperintensity within the supratentorial white matter, mostly subcortical on T2-weighted and fluid-attenuated inversion-recovery. The patient received a diagnosis of SS and was subsequently referred to the neurology service for further assessment and potential treatment. Conclusion and importance: SS may manifest as a presentation of CML. It is advisable to conduct investigations for SS in CML patients experiencing neurological, ophthalmological, or otological symptoms.

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Senile plaque blue autofluorescence was discovered around 40 years ago, however, its impact on Alzheimer's disease (AD) pathology has not been fully examined. We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aß aggregation in vitro. In DAPI or Hoechst staining, the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence. The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted. Both Aß self-oligomers and Aß/hemoglobin heterocomplexes generated blue autofluorescence. The Aß amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation, hemolysis, cerebral amyloid angiopathy, vascular plaques, vascular adhesions, and microaneurysms. In summary, we conclude that Aß-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer's disease.

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OBJECTIVE: To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. DESIGN: Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). PARTICIPANTS: Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. METHODS: A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. MAIN OUTCOME MEASURES: Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. RESULTS: Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016). CONCLUSIONS: Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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Diabetic retinopathy (DR) is a microvascular complication of diabetes. Microaneurysms (MAs) are often observed in the retinal vessels of diabetic patients and represent one of the earliest signs of DR. Accurate and efficient detection of MAs is crucial for the diagnosis of DR. In this study, an automatic model (MA-YOLO) is proposed for MA detection in fluorescein angiography (FFA) images. To obtain detailed features and improve the discriminability of MAs in FFA images, SwinIR was utilized to reconstruct super-resolution images. To solve the problems of missed detection of small features and feature information loss, an MA detection layer was added between the neck and the head sections of YOLOv8. To enhance the generalization ability of the MA-YOLO model, transfer learning was conducted between high-resolution images and low-resolution images. To avoid excessive penalization due to geometric factors and address sample distribution imbalance, the loss function was optimized by taking the Wise-IoU loss as a bounding box regression loss. The performance of the MA-YOLO model in MA detection was compared with that of other state-of-the-art models, including SSD, RetinaNet, YOLOv5, YOLOX, and YOLOv7. The results showed that the MA-YOLO model had the best performance in MA detection, as shown by its optimal metrics, including recall, precision, F1 score, and AP, which were 88.23%, 97.98%, 92.85%, and 94.62%, respectively. Collectively, the proposed MA-YOLO model is suitable for the automatic detection of MAs in FFA images, which can assist ophthalmologists in the diagnosis of the progression of DR.

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Purpose: To describe cases of asymptomatic peripheral retinal hemorrhage attributed to presumed vitreous base traction seen on ultra-widefield (UWF) imaging. Methods: This retrospective consecutive series comprised asymptomatic patients with peripheral retinal hemorrhages, microaneurysms, or both. Imaging included UWF fundus photography, fundus autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT), or a combination. Results: The series included 9 adult patients. The findings were observed on a routine eye examination or as an incidental finding in the contralateral eye of patients presenting with a retinal break or detachment. On UWF imaging, the distinguishing features of the peripheral retinal hemorrhages and microaneurysms presumably caused by vitreous base traction were their pinpoint shape and location at the vitreous base, in particular in the far temporal and superior retinal periphery. UWF FA showed punctate hyperfluorescent spots with no leakage. OCT showed signs of evolving posterior vitreous detachment. Management was limited to observation; with time, the microaneurysms were stable and the hemorrhages resolved. Conclusions: UWF imaging has led to the identification of presumed vitreous base vasculopathy. After a targeted workup is unrevealing, observation is appropriate.

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Background and Objectives: This study aimed to elucidate the role of laser photocoagulation therapy in the treatment of diabetic macular edema (DME) as an alternative to, or in conjunction with, the first-line treatment, anti-vascular endothelial growth factor (VEGF). Materials and Methods: A comprehensive literature search to identify studies that evaluated the efficacy of laser photocoagulation therapy in the management of DME was performed. The relevant findings of the efficacy of focal/grid laser therapy from data in randomized, controlled trials were synthesized, and the potential of new laser technologies, such as navigated laser systems, pattern scan lasers, and subthreshold lasers, was explored. The usefulness of multimodal imaging-guided laser therapy was also evaluated, with a focus on the potential contribution to anti-VEGF therapy. Results: Focal laser photocoagulation targeting microaneurysms remains an effective therapeutic approach to chronic refractory edema, despite the widespread use of anti-VEGF therapy. To achieve the best possible treatment outcomes, precise identification of microaneurysms is essential. This requires the use of multimodal imaging-guided, highly accurate, minimally invasive coagulation techniques. Subthreshold laser therapy can also reduce the frequency of anti-VEGF injections and minimize treatment burden. Conclusions: Further studies are needed to determine the optimal timing and settings for laser photocoagulation therapy and the potential of new laser technologies in the management of DME. Nevertheless, laser photocoagulation therapy plays an important role in the management of DME, in conjunction with anti-VEGF therapy.

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The appropriate surgical technique to improve the closure rate of perioperative full-thickness macular hole (FTMH) secondary to submacular hemorrhage (SMH) with sub-internal limiting membrane (ILM) hemorrhage caused by retinal arterial macroaneurysm (RAM) rupture remains an unsolved clinical problem. Several ILM transplantation techniques have been attempted, but these are challenging. Our new technique can remove sub-ILM hemorrhage with the central fovea ILM intact, without peeling the ILM. The medical records of three eyes from three patients with SMH and sub-ILM hemorrhage secondary to RAM rupture were retrospectively reviewed. During the surgery, a small ILM fissure was made outside the central fovea with ILM forceps, and sub-ILM hemorrhage was washed out through it by manually spraying balanced salt solution. Sub-ILM hemorrhage removal was achieved successfully in all eyes, with no occurrences of FTMH or other complications. Best-corrected decimal visual acuity improved from 0.05 (Snellen equivalent (SE), 20/400), 0.05 (SE, 20/400), and 0.05 (SE, 20/400) preoperatively to 0.3 (SE, 20/63), 0.4 (SE, 20/50), and 0.15 (SE, 20/125) at 3 months postoperatively, respectively. This new technique may help keep the foveal ILM intact and prevent perioperative FTMH formation.

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The aim of this study is to correlate small dot hyper-reflective foci (HRF) observed in spectral domain optical coherence tomography (SD-OCT) scans of an animal model of hyperglycaemia with focal electroretinography (fERG) response and immunolabelling of retinal markers. The eyes of an animal model of hyperglycaemia showing signs of diabetic retinopathy (DR) were imaged using SD-OCT. Areas showing dot HRF were further evaluated using fERG. Retinal areas enclosing the HRF were dissected and serially sectioned, stained and labelled for glial fibrillary acidic protein (GFAP) and a microglial marker (Iba-1). Small dot HRF were frequently seen in OCT scans in all retinal quadrants in the inner nuclear layer or outer nuclear layer in the DR rat model. Retinal function in the HRF and adjacent areas was reduced compared with normal control rats. Microglial activation was detected by Iba-1 labelling and retinal stress identified by GFAP expression in Müller cells observed in discrete areas around small dot HRF. Small dot HRF seen in OCT images of the retina are associated with a local microglial response. This study provides the first evidence of dot HRF correlating with microglial activation, which may allow clinicians to better evaluate the microglia-mediated inflammatory component of progressive diseases showing HRF.

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Introduction: To report a cases series of retinal vascular occlusions with telangiectatic capillaries (TelCaps) seen on indocyanine green angiography (ICGA) and multimodal imaging. Methods: In this case series, a new finding (TelCaps) was seen on clinical examination, fundus evaluation, fluorescein angiography, ICGA, and optical coherence tomography (OCT). Results: This series comprised 3 patients with TelCaps findings on ICGA after retinal vascular occlusions. The patients' ages ranged from 52 years to 71 years and the best-corrected visual acuity in the affected eye, from 20/25 to 20/80. Fundus evaluation showed small, hard exudates in the vascular termination close to the macula with a reduction of the foveal reflex. The OCT images showed marginal hyperreflectivity and inner hyporeflectivity that were suggestive of a TelCaps lesion, which was confirmed by hyperfluorescence in the late phase of ICGA. Conclusions: This study highlights the importance of performing multimodal imaging evaluation, including ICGA, in eyes with retinal vein occlusions for early identification and management of the associated lesions.

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BACKGROUND: Moyamoya disease (MMD) is linked to the formation of intracranial aneurysms. The authors recently observed an effective use of magnetic resonance vessel wall imaging (MR-VWI) to detect de novo unruptured MMD-associated microaneurysms. OBSERVATIONS: The authors describe a 57-year-old female who was diagnosed with MMD 6 years ago after suffering a left putaminal hemorrhage. MR-VWI revealed point-like enhancement in the right posterior paraventricular region during the annual follow-up. On the T2-weighted image, this lesion was surrounded by high intensity. Angiography revealed a microaneurysm in the periventricular anastomosis. Right combined revascularization surgery was performed to prevent future hemorrhagic events. Another de novo circumferential enhanced lesion on MR-VWI appeared in the left posterior periventricular region 3 months after surgery. Angiography revealed that the enhanced lesion was a de novo microaneurysm on the periventricular anastomosis. The left combined revascularization surgery went well. The bilateral microaneurysms vanished on follow-up angiography. LESSONS: Unruptured MMD-associated microaneurysms on the periventricular anastomosis can be detected using MR-VWI. Revascularization surgery can eliminate microaneurysms by reducing hemodynamic stress on the periventricular anastomosis.

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Purpose: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME. Patients and Methods: Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images. Results: There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03). Conclusion: Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.

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Purpose: To explored Relationship between uric acid and cerebral amyloid angiopathy; Materials and methods: ZO-1 and RAGE in HBMECs were detected by western blotting, and then, we analyzed ZO-1, occludin, and RAGE mRNA expression levels in different treatment groups using RTPCR. Cell counts and the relative αSMA fluorescence intensity were measured in order to evaluate the protective effect of uric acid against injury to HBVSMCs. Analysis of variance showed that LDH leakage rate was used to verify the uric acid protective effect on the injury induced by Aß1-40. After that, the level of uric acid in serum and Aß1-40 in brain tissue was analyzed by western blotting and immunohistochemistry to evaluate the protective effect of uric acid in the brain of APP23 mice. Meanwhile, Occludin, ZO-1, and RAGE protein levels were measured by western blotting; Results: Uric acid reduced the negative effects of Aß on the vascular endothelium and smooth muscle cells and protected the vascular wall in vitro. In APP23 mice, Aß1-40 and Aß1-42 levels were significantly elevated in brain tissues and further increased after uric acid concentration was decreased. In APP23 mice, ZO-1 and occludin expression levels were both significantly lower than those in wild-type animals. After uric acid concentration was lowered in APP23 mice, ZO-1 and occludin expression levels were significantly lower than those in untreated animals; Conclusions: Uric acid in the blood protects the blood vessels from CAA damage to the blood vessel wall, and reduces the occurrence of cerebral hemorrhage.

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Senile plaques are a pathological hallmark of Alzheimer's disease (AD), yet the mechanism underlying their generation remains unknown. Beta-amyloid peptide (Aß) is a major component of senile plaques. We analysed AD brain tissues with histochemistry, immunohistochemistry and fluorescence imaging to examine the neural, vascular or blood Aß contribution to senile plaque development. We found little neural marker co-expression with plaque Aß, while co-expression of blood markers, such as Haemin and ApoE, was abundant. The plaque cores were structured with vascular and glial proteins outside and blood metabolites inside, co-localizing with a characteristic of Hoechst staining-independent blue autofluorescence. Erythrocyte-interacting Aß is linked to coagulation, elevated calcium and blue autofluorescence, and it is associated with intravascular haemolysis, atherosclerosis, cerebral amyloid angiopathy, microaneurysm, and often with Cathepsin D co-expression. We identified microaneurysms as major sites of amyloid formation. Our data suggest that senile plaques arise from Aß- and Cathepsin D-enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture.

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Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

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