Effect of microaneurysms on the anti-VEGF treatment for diabetic macular edema: A retrospective cross-sectional study.

Although anti-vascular endothelial growth factor (VEGF) treatment is effective for treating diabetic macular edema (DME), the effect of the microaneurysm (MA) status on the therapeutic efficacy of an anti-VEGF treatment remains unclear. Our current study investigated the effects of the number and the presence or absence of leaking MAs on DME and the efficacy of anti-VEGF therapy. A total of 51 eyes of 47 DME patients were administered anti-VEGF treatment. Fluorescence angiography results were used to determine the number of MAs and the presence or absence of leakage, with these findings matched to the optical coherence tomography maps. The correlation between the number of MAs and the retinal thicknesses and the influence of the leaking MAs was examined in order to definitively determine the effect of the anti-VEGF treatment. There was a correlation between the number of MAs and the retinal thickness of the sector in both the 6 mm (correlation coefficients: 0.42) and 3 mm (0.34) sectors (P < .001). There was also a correlation between the number of MAs and the retinal thickness in both the 6 mm (0.31) and 3 mm (0.24) sectors after undergoing the treatment (P < .01). There was a significant difference between the mean thickness of the leaking versus the non-leaking MAs in the 6 mm (388 ±â€…87 µm) and 3 mm (477 ±â€…108 µm) sectors before treatment (P < .01). There was also a significant difference for the retinal thickness between the sectors with and without leaking MAs after the treatment (P < .01). The degree of retinal edema before treatment is associated with the number of MAs and the presence of leaking MAs. Anti-VEGF treatment is less effective for focal macular edema with large numbers of MAs, which includes leaking MAs.

Diabetic microaneurysms detected by fluorescein angiography spatially correlate with regions of macular ischemia delineated by optical coherence tomography angiography.

Purpose: To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs) identified by fundus fluorescein angiography (FFA). Methods: Patients with diabetic retinopathy (DR) who underwent OCTA and FFA were retrospectively identified. FFA images were cropped and aligned with their respective OCTA images using i2k Align Retina software (Dual-Align, Clifton Park, NY, USA). Foveal avascular zone (FAZ) and ischemic areas were manually delineated on OCTA images, and MAs were marked on the corresponding FFA images before overlaying paired scans for analysis (ImageJ; National Institutes of Health, Bethesda, MD, USA). Results: Twenty-eight eyes of 20 patients were included. The average number of MAs identified in cropped FFA images was 127 ± 42. More DMI was noted in the superficial capillary plexus (SCP; 36 ± 13%) compared to the deep capillary plexus (DCP; 28 ± 14%, P < 0.001). Similarly, more MAs were associated with ischemic areas in SCP compared to DCP (92.0 ± 35.0 vs. 76.8 ± 36.5, P < 0.001). Most MAs bordered ischemic areas; fewer than 10% localized inside these regions. As DMI area increased, so did associated MAs (SCP: r = 0.695, P < 0.001; DCP: r = 0.726, P < 0.001). Density of MAs surrounding FAZ (7.7 ± 6.0 MAs/mm2) was similar to other DMI areas (SCP: 7.0 ± 4.0 MAs/mm2, P = 0.478; DCP: 9.2 ± 10.9 MAs/mm2, P = 0.394). Conclusion: MAs identified in FFA strongly associate with, and border areas of, DMI delineated by OCTA. Although more MAs are localized to SCP ischemia, the concentration of MAs associated with DCP ischemia is greater. By contrast, few MAs are present inside low-flow regions, likely because capillary loss is associated with their regression.

Confocal MultiColor Signal Depends on Perfusion Characteristics of Retinal Microaneurysms in Diabetic Retinopathy as Detected by OCTA.

Purpose: To propose a noninvasive way of classifying multimodal imaging of retinal microaneurysms (MA) secondary to diabetic retinopathy (DR). Methods: The research was designed as a cross-sectional, observational study of patients affected by DR. Multimodal imaging included confocal MultiColor imaging, optical coherence tomography (OCT) and OCT angiography (OCTA). MA green- and infrared-reflectance components were assessed by confocal MultiColor imaging, reflectivity properties by OCT, and MA perfusion features by OCTA. In addition, we included high-resolution (HR) and high-speed (HS) OCTA scans to assess HR-HS agreement in detecting retinal MA and to highlight different perfusion features detected by both OCTA acquisitions. Results: We analyzed 216 retinal MAs, divided into green (46; 21%), red (58; 27%) and mixed types (112; 52%). Green MAs were mainly hyper-reflective on OCT, with no or poor filling on OCTA. Red MAs were characterized by an isoreflective signal on OCT and full filling on OCTA. Mixed MAs showed a hyper-reflective border and a hyporeflective core on OCT and partial filling on OCTA. No differences in red MA HR/HS size discrepancy and reflectivity were found, whereas these progressively increased as the MA MultiColor signal changed from infrared to green. MA types significantly correlated with visual acuity, DR duration, and DR severity. Conclusions: Retinal MA can be classified reliably by means of a fully noninvasive multimodal imaging-based assessment. MA types are matched with visual acuity, DR duration and DR severity. Both HR and HS OCTA are highly effective in detecting MA, although HR OCTA is to be preferred in the presence of fibrotic evolution. Translational Relevance: This study outlines a proposed novel MA classification based on noninvasive multimodal imaging. The findings presented in this paper endorse the clinical relevance of this approach, highlighting how this classification is associated with both DR duration and severity.

The comparative effects of oral Chinese patent medicines in non-proliferative diabetic retinopathy: A Bayesian network meta-analysis of randomized controlled trials.

Background: Non-proliferative diabetic retinopathy (NPDR), a common diabetic complication with high morbidity, is featured by impaired visual function and fundus lesions. It has been reported that oral Chinese patent medicines (OCPMs) may improve visual acuity and fund signs. However, the best possible OCPMs for NPDR remain questionable and merit further investigation. Methods: From inception to October 20, 2022, seven databases were searched for eligible randomized controlled trials (RCTs). The outcomes were clinical effective rate, visual acuity, visual field gray value, microaneurysm volume, hemorrhage area, macular thickness, and adverse events rate. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the quality of the included studies. Network meta-analysis was performed using R 4.1.3 and STATA 15.0 software. Results: We included 42 RCTs with 4,858 patients (5,978 eyes). The Compound Danshen Dripping Pill (CDDP) combined with calcium dobesilate (CD) had the most improvement in clinical efficacy rate (SUCRA, 88.58%). The Compound Xueshuantong Capsule (CXC) combined with CD may be the best intervention (SUCRA, 98.51%) for the improvement of visual acuity. CDDP alone may be the most effective treatment option (SUCRA, 91.83%) for improving visual field gray value. The Hexuemingmu Tablet (HXMMT) and Shuangdan Mingmu Capsule (SDMMC) combined with CD may be the most effective treatment for reducing microaneurysm volume and hemorrhage area (SUCRA, 94.48%, and 86.24%), respectively. Referring to reducing macular thickness, CXC combined with CD ranked first (SUCRA, 86.23%). Moreover, all OCPMs did not cause serious adverse reactions. Conclusion: OCPMs are effective and safe for NPDR. CDDP alone, and combined with CD, may be the most effective in improving visual field gray value and clinical efficacy rate, respectively; CXC combined with CD may be the best in enhancing BCVA and reducing macular thickness; HXMMT and SDMMC combined with CD, maybe the most effective regarding microaneurysm volume and hemorrhage area, respectively. However, the reporting of methodology in the primary study is poor, potential biases may exist when synthesizing evidence and interpreting the results. The current findings need to be confirmed by more large-sample, double-blind, multi-center RCTs of rigorous design and robust methods in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022367867.

Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review.

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.

Automatic detection of microaneurysms in optical coherence tomography images of retina using convolutional neural networks and transfer learning.

Microaneurysms (MAs) are pathognomonic signs that help clinicians to detect diabetic retinopathy (DR) in the early stages. Automatic detection of MA in retinal images is an active area of research due to its application in screening processes for DR which is one of the main reasons of blindness amongst the working-age population. The focus of these works is on the automatic detection of MAs in en face retinal images like fundus color and Fluorescein Angiography (FA). On the other hand, detection of MAs from Optical Coherence Tomography (OCT) images has 2 main advantages: first, OCT is a non-invasive imaging technique that does not require injection, therefore is safer. Secondly, because of the proven application of OCT in detection of Age-Related Macular Degeneration, Diabetic Macular Edema, and normal cases, thanks to detecting MAs in OCT, extensive information is obtained by using this imaging technique. In this research, the concentration is on the diagnosis of MAs using deep learning in the OCT images which represent in-depth structure of retinal layers. To this end, OCT B-scans should be divided into strips and MA patterns should be searched in the resulted strips. Since we need a dataset comprising OCT image strips with suitable labels and such large labelled datasets are not yet available, we have created it. For this purpose, an exact registration method is utilized to align OCT images with FA photographs. Then, with the help of corresponding FA images, OCT image strips are created from OCT B-scans in four labels, namely MA, normal, abnormal, and vessel. Once the dataset of image strips is prepared, a stacked generalization (stacking) ensemble of four fine-tuned, pre-trained convolutional neural networks is trained to classify the strips of OCT images into the mentioned classes. FA images are used once to create OCT strips for training process and they are no longer needed for subsequent steps. Once the stacking ensemble model is obtained, it will be used to classify the OCT strips in the test process. The results demonstrate that the proposed framework classifies overall OCT image strips and OCT strips containing MAs with accuracy scores of 0.982 and 0.987, respectively.

Comparison of multicolor scanning laser ophthalmoscopy and optical coherence tomography angiography for detection of microaneurysms in diabetic retinopathy.

This study aimed to evaluate the usefulness of multicolor (MC) scanning laser ophthalmoscopy (MC-SLO) in detecting microaneurysm (MA) in eyes with diabetic retinopathy (DR). This was a retrospective cross-sectional study. Eyes with DR underwent fluorescein angiography (FA), MC-SLO, optical coherence tomography angiography (OCTA), and color fundus photography (CFP) were analyzed. The foveal region was cut in an 6 × 6 mm image and the number of MA in each image was counted by retina specialists to determine the sensitivity and positive predictive value. FA results were used as the ground standard. MAs were classified as those with early, late, or no dye leakage based on FA images. Fifty-four eyes of 35 patients with an average age of 64.5 ± 1.24 years were included. The sensitivity of MA detection was 37.3%, 15.3%, and 4.12% in MC-SLO, OCTA, and CFP, respectively (P < 0.01 in each pair).The positive predictive value was 66.4%, 46.4%, and 27.6% in MC, OCTA, and CFP, respectively (P < 0.01 in each pair). Sensitivity for MAs with early leakage was 36.4% in MC-SLO, which was significantly higher than 4.02% in OCTA. MC-SLO was more useful in detecting MA in eyes with DR than OCTA.

Identification of microvascular and morphological alterations in eyes with central retinal non-perfusion.

PURPOSE: To evaluate the characteristics and morphological alterations in central retinal ischemia caused by diabetic retinopathy (DR) or retinal vein occlusion (RVO) as seen in optical coherence tomography angiography (OCTA) and their relationship to visual acuity. METHODS: Swept-source optical coherence tomography (SSOCT) and OCTA (Topcon, Triton) data of patients with central involving retinal ischemia were analyzed in this cross-sectional study. The following parameters were evaluated: vessel parameters, foveal avascular zone (FAZ), intraretinal cysts (IRC), microaneurysms (MA), vascular collaterals in the superficial (SCP) and deep plexuses (DCP), hyperreflective foci (HRF), epiretinal membrane (ERM), external limiting membrane (ELM) and ellipsoid zone (EZ) disruption, as well as the disorganization of retinal inner layers (DRIL). Best-corrected visual acuity (BCVA), age, gender, disease duration and ocular history were also recorded. RESULTS: 44 eyes of 44 patients (22 with RVO, 22 with DR) were analyzed. The mean age was 60.55 ± 11.38 years and mean BCVA 0.86 ± 0.36 (Snellen, 6m). No significant difference was found between DR subgroups (non proliferative vs. proliferative). Between RVO subgroups (CRVO vs. BRVO) a significant difference was found in term of collateral vessel of the DCP (p = 0.014). A pooled DR and RVO group were created and compared. Significantly more MAs (p = 0.007) and ERM (p = 0.007) were found in the DR group. Statistically significant negative correlation was demonstrated between FAZ and BCVA (p = 0.45) when analyzing all patients with retinal ischemia. CONCLUSION: This study has shown that the best predictor of visual outcome in center involved ischemic diseases is the size of FAZ. Besides the presence of MAs and ERM, all other OCT and OCTA parameters were present in a similar extent in DR and RVO group despite the completely different disease origins. Our results suggest that as soon as retinal ischemia in the macular region is present, it has a similar appearance and visual outcome independently of the underlying disease.

Retinopathy Analysis Based on Deep Convolution Neural Network.

At medical checkups or mass screenings, the fundus examination is effective for early detection of systemic hypertension, arteriosclerosis, diabetic retinopathy, etc. In most cases, ophthalmologists and physicians grade retinal images by the condition of the blood vessels, lesions. However, human observation does not provide quantitative results, thus blood vessel analysis is an important process in determining hypertension and arteriosclerosis, quantitatively. This chapter describes the latest automated blood vessel extraction using the deep convolution neural network (DCNN). Diabetic retinopathy is a common cardiovascular disease and a major factor in blindness. Therefore, early detection of diabetic retinopathy is very important to preventing blindness. A microaneurysm is an initial sign of diabetic retinopathy, and much research has been conducted for microaneurysm detection. This chapter also describes diabetic retinopathy detection and automated microaneurysm detection using the DCNN.

Spontaneous liver rupture secondary to distal right hepatic artery microaneurysms in a patient admitted due to Staphylococcus aureus pneumonia

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Treatment of macular hemorrhage in retinal arterial microaneurysm: anatomic site-oriented therapy.

PURPOSE: To investigate the usefulness of anatomic site-oriented therapy for macular hemorrhage secondary to retinal arterial macroaneurysm (RAM). STUDY DESIGN: Retrospective observational study, clinical case series METHODS: Twenty-seven consecutive patients (27 eyes) with macular hemorrhage secondary to RAM were classified according to the retinal layer(s) with hemorrhage identified by optical coherence tomography into 4 types and treated differentially. Vitrectomy was conducted for subinternal limiting membrane hemorrhage (SILMH), intravitreal gas injection for subretinal hemorrhage (SRH) or intraretinal hemorrhage (IRH), and vitrectomy and intravitreal air/gas exchange for multilevel hemorrhage (at least 2 among SILMH/SRH/IRH). RESULTS: Complete displacement or resolution of the macular hemorrhage was achieved in all 27 eyes: 7 with SILMH, 7 with SRH, 3 with IRH, and 10 with multilevel hemorrhage. Compared with the baseline score, the 3-month postoperative Early Treatment Diabetic Retinopathy Study score (mean ± SD) improved significantly in SILMH (+42.9 ± 6.9 letters; P < .0001, paired t test), multilevel hemorrhage (+23.9 ± 14.4 letters; P = .0005), and SRH (+17.7 ± 18.4 letters; P = .0440), but not in IRH (+6.7 ± 9.0 letters; P = .3228). Compared with the baseline thickness, the 3-month postoperative central retinal thickness decreased significantly in multilevel hemorrhage (-930.3 ± 290.8 µm; P < .0001), SILMH (-628.4 ± 177.0 µm; P < .0001), IRH (-508.3 ± 72.1 µm; P = .0066), and SRH (-476.9 ± 300.0 µm; P = .0056). The central ellipsoid zone was detectable in 7/7 eyes with SILMH but in none of the eyes in the other 3 groups (P < .0001). No retinal detachment or macular hole occurred in any eyes. CONCLUSION: For macular hemorrhage secondary to RAM, anatomic site-oriented therapy using different treatments targeting the hemorrhagic retinal layers is useful. The optimal treatments for individual hemorrhagic retinal layers require further studies.

Spontaneous liver rupture secondary to distal right hepatic artery microaneurysms in a patient admitted due to Staphylococcus aureus pneumonia.

Spontaneous liver rupture is an uncommon and life-threatening condition often associated with high mortality rate. The most common causes are preeclampsia and HELLP syndrome during pregnancy, liver tumours and overdosing of anticoagulant therapy, however, hepatic rupture in the absence of underlying pathology is an extremely rare occurrence. Treatment can include observation, embolization, hepatic artery ligation, hepatic lobectomy, hematoma evacuation and packing, and even liver transplantation has been described.

A case of Leber's miliary aneurysms with diffuse peripheral retinal vascular sheathing.

A 30-year-old female presented with macular edema and discoid exudation at the posterior pole. Diffuse vascular sheathing was observed at the peripheral retina. Fluorescein angiography revealed multiple microaneurysms at the posterior pole and leakage from the peripheral vessels. Two monthly intravitreal bevacizumab led to minimal improvement, and resolution of macular edema was achieved by an additional intravitreal triamcinolone. The findings at the posterior pole resembled those of Leber's miliary aneurysm. However, this case also demonstrated a peculiar vascular sheathing at the periphery and showed response to triamcinolone, which are evidences for an inflammatory condition.

Clinical and Angiographic Characteristics of 35 Patients With Cryptogenic Hemoptysis.

BACKGROUND: Hemoptysis can cause a life-threatening condition and often needs to be treated urgently. Nearly 20% of hemoptysis cases are diagnosed as cryptogenic after clinical investigation. The purpose of this study was to clarify the clinical and angiographic characteristics of cryptogenic hemoptysis. METHODS: We retrospectively reviewed medical records of 35 patients admitted to our hospital with cryptogenic hemoptysis from October 2010 to September 2014. RESULTS: In the 35 cases, bronchial artery embolization was successfully performed in 33 patients (94.3%), whereas bronchoscopic hemostatic therapy was added in one patient (2.8%), and embolization was not performed in one patient (2.8%) because the bronchial artery was too narrow. In the successful embolization group, the non-rebleeding rate was 97.0% for 20 months. The angiographic findings revealed that the diameter of the bronchial arteries was < 2 mm in 13 patients, 2 to 3 mm in 17 patients, and > 3 mm in five patients. Hypervascularization was detected in 29 patients (82.9%) and small bronchial aneurysms in eight patients (22.9%). The amount of hemoptysis was slight (< 50 mL/d) in 12, mild (50-100 mL/d) in 11, moderate (100-200 mL/d) in eight, and massive (> 200 mL/d) in four patients. No obvious relationship was found between the diameter of bronchial arteries and the amount of hemoptysis. CONCLUSIONS: BAE was highly effective for the management of cryptogenic hemoptysis. Most cases of cryptogenic hemoptysis have angiographic abnormalities, including small or microaneurysms, which were suspected as the cause in some cases.

[Hemorrhagic shock revealing multiple digestive microaneurysms in a patient with systemic lupus erythematosus: Case report and literature review]. / Choc hémorragique révélant des micro-anévrismes digestifs au cours du lupus : cas clinique et revue de la littérature.

INTRODUCTION: The vascular disorders in systemic lupus erythematosus (SLE) result from various mechanisms and presentations (inflammatory disease or vasculitis, atherosclerosis). CASE REPORT: We report on a 34-year-old man with cutaneous, articular, neurological and nephrologic SLE. He presented with catastrophic haemorrhage on microaneurysm rupture of the left hepatic artery. After blood transfusions and immunosuppressive treatments, his condition improves. CONCLUSION: Uncommon complication in SLE patients, digestive vasculitis with microaneurysms may occur as in polyarteritis nodosa. In the literature, we identified 10 additional cases of hepatic microaneurysms in SLE patients. The main issue is an earlier diagnosis in order to give appropriate treatment and improve prognosis.

Retinal Sensitivity in Patients with Type I Diabetes without Retinopathy or with Minor Retinal Changes.

Objective: To evaluate the ability of short-wavelength automated perimetry (SWAP) for the detection of visual impairment in patients with type I diabetes without retinopathy or with minor retinal vascular changes. Design: Comparative cross-sectional study. Participants: 30 eyes of 30 healthy subjects and 73 eyes of 73 patients with type I diabetes mellitus were studied. Methods: Ophthalmic examination of diabetic patients showed no retinopathy or minimal changes (less than 5 microaneurisms in each eye) with no previous laser treatment. All patients were examined by means of the SWAP 24-2 strategy. Mean Deviation (MD) and Pattern Standard Deviation (PSD) were compared between both groups. Results: There were differences in the clusters of altered points between both groups (p=0.004). SWAP MD was lower in the diabetic group than in the controls (-2.89 dB vs. -0.20 dB, p<0.001). SWAP PSD also differed between both groups (2.50 dB in control group, 3.12 dB in the diabetic group, p=0.003). In the diabetic group, mean period from the onset of diabetes was 12.6±6.7 years and minimal vascular changes were observed in the retina of 18 eyes (24.7%), while 55 had no lesions (75.3%). No differences in SWAP changes were found between patients without and with minimal diabetic retinopathy. Conclusions: Retinal sensitivity assessed by SWAP is depressed in patients with type I diabetes regardless of the presence of retinal vascular changes.

Microaneurysms cause refractory macular edema in branch retinal vein occlusion.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents can treat macular edema (ME) in branch retinal vein occlusion (BRVO). However, refractory ME, the mechanism of which is not well elucidated, occurs frequently. Sixty-six eyes with ME secondary to BRVO were enrolled in this retrospective observational case-control study. Twenty eyes received a sub-Tenon's capsule injection of triamcinolone acetonide (STTA), 22 eyes an intravitreal anti-VEGF injection (ranibizumab), 16 eyes were switched from STTA to ranibizumab, 4 eyes underwent vitrectomy, and 4 eyes were untreated. Multiple regression analysis and multivariate logistic regression analysis were conducted, respectively, to identify independent predictors of visual acuity (VA) prognosis and risk factors for refractory ME longer than 1 year. The mechanism of refractory ME and therapeutic approaches for identified risk factors also were investigated. Thirty-four (52%) eyes had refractory ME for over 1 year. Microaneurysms were identified as risk factors for refractory ME, leading to poor final VA. Ranibizumab suppressed microaneurysm formation and refractory ME, with early administration more effective. For already formed microaneurysms, laser photocoagulation reduced additional treatments. Microaneurysms may cause refractory ME in BRVO. Alternative therapy to suppress microaneurysms should be considered to prevent refractory ME in patients with BRVO.