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American Journal of Ophthalmology Case... Mar 2024To report two cases of diabetic macular edema (DME) treated with intravitreal faricimab injections (IVFs), including the assessment of retinal microaneurysms and extent...
PURPOSE
To report two cases of diabetic macular edema (DME) treated with intravitreal faricimab injections (IVFs), including the assessment of retinal microaneurysms and extent of retinal capillary non-perfusion using fluorescein angiography (FA) and indocyanine green angiography (IA).
OBSERVATIONS
Case 1: A 72-year-old man presented with aflibercept-resistant DME in the left eye, with a best-corrected visual acuity (BCVA) of 20/16. FA showed areas of retinal capillary non-perfusion and focal leakage in the macular area of the left eye. IA revealed numerous microaneurysms in the temporal region of the macula. Four consecutive monthly IVFs were administered to the left eye, and DME eventually diminished. After the loading phase, the BCVA was maintained at 20/16 with reduced visual distortion. FA showed improvement of macular leakage and stable retinal capillary non-perfusion areas, and the foveal avascular zone was clearly observed. The disappearance of numerous microaneurysms was confirmed on IA images.Case 2: An 80-year-old woman developed DME with macular vein occlusion in the left eye after panretinal laser photocoagulation for proliferative diabetic retinopathy. The patient's BCVA was 20/32. DME was resistant to subtenon triamcinolone injections. FA revealed focal areas of retinal capillary non-perfusion and persistent leakage in the macular area of the left eye. IA revealed scattered microaneurysms within the retinal arcade. Four consecutive monthly IVFs were administered to the left eye, and DME eventually diminished. After the loading phase, the BCVA was maintained at 20/32. FA showed improvement of macular leakage and stable retinal capillary non-perfusion areas. The reduction of microaneurysms was confirmed on IA images.
CONCLUSIONS AND IMPORTANCE
These case reports highlight the potential of faricimab as an alternative anti-vascular endothelial growth factor drug for treatment-resistant DME, including reduction of retinal microaneurysms and stabilization of the areas of retinal capillary non-perfusion. However, continuation of a robust treatment regimen may be required to achieve these objectives.
PubMed: 38116329
DOI: 10.1016/j.ajoc.2023.101973 -
Medical & Biological Engineering &... May 2024Most diabetes patients are liable to have diabetic retinopathy (DR); however, the majority of them might not be even aware of the ailment. Therefore, early detection and...
Most diabetes patients are liable to have diabetic retinopathy (DR); however, the majority of them might not be even aware of the ailment. Therefore, early detection and treatment of DR are necessary to prevent vision loss. But, avoiding DR is not a simple process. An ophthalmologist can typically identify DR through an optical evaluation of the fundus and through the evaluation of color pictures. However, due to the increased count of DR patients, this could not be possible as it consumes more time. To rectify this problem, a novel deep ensemble-based DR classification technique is developed in this work. Initially, a Wiener filter (WF) is applied for preprocessing the image. Then, the enhanced U-Net-based segmentation process is done. Subsequent to the segmentation process, features are extracted that include statistical features, inferior superior nasal temporal (ISNT), cup to disc ratio (CDR), and improved LGBP as well. Further, deep ensemble classifiers (DEC) like CNN, Bi-GRU, and DMN are used to recognize the disease. The outcomes from DMN, CNN, and Bi-GRU are then subjected to improved SLF. Additionally, the weights of DMN, CNN, and Bi-GRU are adjusted via pelican updated Tasmanian devil optimization (PU-TDO). Finally, outputs on DR (microaneurysms, hemorrhages, hard exudates, and soft exudates) are obtained. The performance of DEC + PU-TDO for diabetic retinopathy is computed over extant models with regard to different measures for four datasets. The results on accuracy using the DEC + PU-TDO scheme for the IDRID dataset is maximum around 0.975 at 90th LP while other models have less accuracy. The FPR of DEC + PU-TDO is less around 0.039 at the 90th LP for the SUSTech-SYSU dataset, while other extant models have maximum FPR.
PubMed: 38713340
DOI: 10.1007/s11517-024-03076-1 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and... (Review)
Review
Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively.
Topics: Humans; Diabetic Retinopathy; Animals; Molecular Targeted Therapy; Cell- and Tissue-Based Therapy; Vascular Endothelial Growth Factor A
PubMed: 38948520
DOI: 10.3389/fendo.2024.1416668 -
Current Vascular Pharmacology Apr 2024Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or...
BACKGROUND
Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore, there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR. Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol, hexosamine, advanced glycation end products, and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances, notably brain-derived neurotrophic factor and nerve growth factor, also play a role in early neurodegeneration, and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration. Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis, glial cell reactivity, and glutamate excitotoxicity. Therefore, inhibitors of these pathways are potential therapeutic avenues. Vascular Component: The nitric oxide pathway, critical for neurovascular coupling, is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF), a long-known angiogenic factor, has demonstrated both damaging and neuroprotective effects, prompting a careful consideration of long-term anti-VEGF therapy.
CONCLUSION
Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.
PubMed: 38693745
DOI: 10.2174/0115701611272737240426050930 -
Microvascular Research Jul 2024Dysfunctional pericytes and disruption of adherens or tight junctions are related to many microvascular diseases, including diabetic retinopathy. In this context,... (Comparative Study)
Comparative Study
Dysfunctional pericytes and disruption of adherens or tight junctions are related to many microvascular diseases, including diabetic retinopathy. In this context, visualizing retinal vascular architecture becomes essential for understanding retinal vascular disease pathophysiology. Although flat mounts provide a demonstration of the retinal blood vasculature, they often lack a clear view of microaneurysms and capillary architecture. Trypsin and elastase digestion are the two techniques for isolating retinal vasculatures in rats, mice, and other animal models. Our observations in the present study reveal that trypsin digestion impacts the association between pericytes and endothelial cells. In contrast, elastase digestion effectively preserves these features in the blood vessels. Furthermore, trypsin digestion disrupts endothelial adherens and tight junctions that elastase digestion does not. Therefore, elastase digestion emerges as a superior technique for isolating retinal vessels, which can be utilized to collect reliable and consistent data to comprehend the pathophysiology of disorders involving microvascular structures.
Topics: Animals; Pancreatic Elastase; Trypsin; Retinal Vessels; Mice, Inbred C57BL; Pericytes; Endothelial Cells; Tight Junctions; Mice; Male
PubMed: 38521153
DOI: 10.1016/j.mvr.2024.104682 -
International Journal of General... 2023Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores...
BACKGROUND AND AIM
Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores whether the effect of those factors is modified by diabetes mellitus (DM) duration.
METHODS
A total of 1058 DM patients with information about DR assessment were included. DR was measured by a complete ophthalmic examination and was classified as having one or more distinct microaneurysms in the eyes. Data from the lab and clinical factors were gathered. Multivariate logistic analysis was used to examine the risk factors, and the best-fitting model was selected by a backward stepwise based on A1C.
RESULTS
In the current study, 274 (25.9%) patients developed DR. In the entire subjects, baseline age, the level of C-peptide, and urinary creatinine were all presented as protective effects of DR, whose odds ratios (ORs) and 95% confidence intervals (CIs) were 0.79 (0.62, 0.99), 0.75 (0.61, 0.91), and 0.70 (0.52, 0.93), respectively. Conversely, systolic pressure (SBP), urinary albumin, and BUN/Cr ratio were the important risk factors for DR with ORs (95% CIs) 1.21 (1.01, 1.46), 1.55 (1.30, 1.84), and 1.33 (1.11, 1.59), respectively. In stratification analysis, females with higher SBP would be more likely to develop DR in the short-duration group, while C-peptide and urinary creatinine showed protective effects in the long-duration group. BUN/Cr ratio all presented as a risk factor, with ORs 1.38 (p = 0.041) and 1.33 (p = 0.014) in short- and long-duration groups, respectively.
CONCLUSION
Although renal functions presented a significant association with DR in all DM patients, the risk factors of DR varied widely in different disease-duration subjects. Target strategies to prevent DR should be put forward individually, considering the patient's DM duration. Improving the BUN/Cr ratio may be beneficial to delaying DR.
PubMed: 37700740
DOI: 10.2147/IJGM.S420983 -
International Journal of Retina and... Jan 2024Diabetic retinopathy (DR) is a leading cause of blindness and involves retinal capillary damage, microaneurysms, and altered blood flow regulation. Optical coherence...
BACKGROUND
Diabetic retinopathy (DR) is a leading cause of blindness and involves retinal capillary damage, microaneurysms, and altered blood flow regulation. Optical coherence tomography angiography (OCTA) is a non-invasive way of visualizing retinal vasculature but has not been used extensively to study blood flow heterogeneity. The purpose of this study is to detect and quantify blood flow heterogeneity utilizing en-face swept source OCTA in patients with DR.
METHODS
This is a prospective clinical study which examined patients with either type 1 or 2 diabetes mellitus. Each included eye was graded clinically as no DR, mild DR, or moderate-severe DR. Ten consecutive en face 6 × 6 mm foveal SS-OCTA images were obtained from each eye using a PLEX Elite 9000 (Zeiss Meditec, Dublin, CA). Built-in fixation-tracking, follow-up functions were utilized to reduce motion artifacts and ensure same location imaging in sequential frames. Images of the superficial and deep vascular complexes (SVC and DVC) were arranged in temporal stacks of 10 and registered to a reference frame for segmentation using a deep neural network. The vessel segmentation was then masked onto each stack to calculate the pixel intensity coefficient of variance (PICoV) and map the spatiotemporal perfusion heterogeneity of each stack.
RESULTS
Twenty-nine eyes were included: 7 controls, 7 diabetics with no DR, 8 mild DR, and 7 moderate-severe DR. The PICoV correlated significantly and positively with DR severity. In patients with DR, the perfusion heterogeneity was higher in the temporal half of the macula, particularly in areas of capillary dropout. PICoV also correlates as expected with the established OCTA metrics of perfusion density and vessel density.
CONCLUSION
PICoV is a novel way to analyze OCTA imaging and quantify perfusion heterogeneity. Retinal capillary perfusion heterogeneity in both the SVC and DVC increased with DR severity. This may be related to the loss of retinal capillary perfusion autoregulation in diabetic retinopathy.
PubMed: 38273321
DOI: 10.1186/s40942-024-00528-6 -
Journal of Clinical Medicine Jan 2024: The aim in this study was to investigate the localization of diabetic retinopathy features at the posterior pole. : This study extracted diabetic retinopathy feature...
: The aim in this study was to investigate the localization of diabetic retinopathy features at the posterior pole. : This study extracted diabetic retinopathy feature locations from 757 macula-centered 45-degree fundus photographs in the publicly available DDR dataset. Arteriole and venule locations were also extracted from the RITE (n = 35) and IOSTAR (n = 29) datasets. Images were normalized to collocate optic disc and macula positions, and feature positions were collated to generate a frequency distribution matrix. Sørensen-Dice coefficients were calculated to compare the location of different features. : Arterioles occurred in two main, distinct arcuate patterns. Venules showed a more diffuse distribution. Microaneurysms were diffusely located around the posterior pole. Hemorrhages and exudates occurred more frequently at the temporal aspect of the macula. Cotton wool spots occurred in a region approximating the radial peripapillary capillaries. Intraretinal microvascular abnormalities and neovascularization were seen throughout the posterior pole, with neovascularization at the disc (n = 65) being more common than neovascularization elsewhere (n = 46). Venous beading occurred primarily between the first and third bifurcations of the venules. Diabetic retinopathy overall was more frequent in the temporal aspect of the macula. The location of cotton wool spots and exudates showed moderate similarity (0.52) when all data were considered, reducing to low similarity (0.18) when areas of low frequency were removed. : Diabetic retinopathy occurs throughout the posterior pole but is more frequent in the temporal aspect of the macula. Understanding the location of diabetic retinopathy features may help inform visual search strategies for diabetic retinopathy screening.
PubMed: 38337501
DOI: 10.3390/jcm13030807 -
Retina (Philadelphia, Pa.) Dec 2023We sought to develop an efficient method for fluorescein angiography (FA) during digitally assisted vitreoretinal surgery (DAVS).
PURPOSE
We sought to develop an efficient method for fluorescein angiography (FA) during digitally assisted vitreoretinal surgery (DAVS).
METHODS
A 485-nm bandpass filter was placed into the filter holder of the accessory light sources of the Constellation Vision System with steel modified washers to produce an exciter source. A barrier filter was placed into the blank slot of a switchable laser filter with a 535-nm bandpass filter and another washer or created digitally with a specific color channel using NGENUITY software version 1.4. Fluorescein, 250 to 500 mg, was then injected intravenously during retinal surgery.
RESULTS
These fluorescence patterns accurately detect many fluorescein angiography biomarkers, such as determination of vascular filling times, ischemia, neovascularization, shunt vessels, microaneurysms, and leakage into the vitreous. This enhanced surgical visualization permitted intervention in real time such as laser or diathermy to residual microvascular abnormalities after delamination of retinal neovascularization as well as heavier panretinal laser placement in areas of retinal capillary dropout to relatively preserve areas of more intact retinal microcirculation.
CONCLUSION
The authors of this study are the first to report an efficient method that permits high-resolution detection of many classic FA biomarkers such as during DAVS to enhance surgical visualization and intervention in real time.
Topics: Humans; Fluorescein Angiography; Retinal Vessels; Retina; Retinal Neovascularization; Vitreous Body; Fluorescein
PubMed: 37026783
DOI: 10.1097/IAE.0000000000003790 -
The Egyptian Heart Journal : (EHJ) :... Jun 2024The reported prevalence of patent foramen ovale (PFO) in the general population is variable. It ranges between 8.6 and 42% according to the population studied and the...
BACKGROUND
The reported prevalence of patent foramen ovale (PFO) in the general population is variable. It ranges between 8.6 and 42% according to the population studied and the imaging technique used. We aim to prospectively assess the prevalence and characteristics of PFO and interatrial septum (IAS) abnormalities as well as the related clinical manifestations in a sample of Egyptian population.
RESULTS
This study comprised 1000 patients who were referred for CT coronary angiography (CTCA). Mean age was 52.5 ± 10.9 years. The prevalence of PFO among the studied population was 16.3%; closed PFO (grade I) 44.2%, open PFO (grade II) 50.9%, and open PFO with jet (grade III) 4.9%. Anatomical high-risk PFO features-defined as the presence of at least 2 or more of the following (diameter ≥ 2 mm, length ≥ 10 mm, septal aneurysm "ASA", or redundant septum)-were found in 51.5% of PFOs' population. Other IAS abnormalities as redundant septum (8.6%), ASA (5.3%), Bachmann's bundle (4.5%), microaneurysm (2.6%), and atrial septal defect (ASD) (0.4%) were detected. There was a lower rate of coexistence of ASA with PFO (p = 0.031). Syncope was significantly higher in patients with PFO compared to those without PFO (6.7% vs. 1.6%, p = 0.001). Stroke, transient ischaemic attacks (TIA), and dizziness were similar in both groups. TIA, dizziness, and syncope were significantly higher in patients with IAS abnormalities including PFO compared to those without IAS abnormalities. Syncope was also significantly higher in PFO with high-risk anatomical features compared to those with non-high-risk PFO population (p = 0.02).
CONCLUSION
The prevalence of PFO in our study was approximately 16.3%, almost half of them showed anatomical high-risk features for stroke. Dizziness, syncope and TIA were significantly higher in patients with IAS abnormalities including PFO.
PubMed: 38856789
DOI: 10.1186/s43044-024-00504-3