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Nature Communications Jun 2024Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of...
Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.
Topics: Humans; Retinal Degeneration; Male; Female; Tomography, Optical Coherence; Adult; Middle Aged; Disease Progression; Multiple Sclerosis, Relapsing-Remitting; Retina; Multiple Sclerosis, Chronic Progressive; Magnetic Resonance Imaging; Prognosis; Nerve Fibers; Retinal Ganglion Cells
PubMed: 38897994
DOI: 10.1038/s41467-024-49309-7 -
International Journal of Ophthalmology 2024With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential... (Review)
Review
With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.
PubMed: 38895690
DOI: 10.18240/ijo.2024.06.20 -
International Journal of Ophthalmology 2024To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular...
AIM
To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line.
METHODS
Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of and , , , genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR).
RESULTS
The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of , , , , and after treatment with both free and niosomal AUR.
CONCLUSION
Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.
PubMed: 38895680
DOI: 10.18240/ijo.2024.06.06 -
Journal of Clinical Medicine May 2024: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal...
: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal diseases. : High-resolution OCT scans from the publicly available Kaggle dataset and a local dataset were used by four state-of-the-art self-supervised frameworks. The backbone model of all the frameworks was a pre-trained convolutional neural network (CNN), which enabled the extraction of meaningful features from OCT images. Anomalous images included choroidal neovascularization (CNV), diabetic macular edema (DME), and the presence of drusen. Anomaly detectors were evaluated by commonly accepted performance metrics, including area under the receiver operating characteristic curve, F1 score, and accuracy. : A total of 25,315 high-resolution retinal OCT slabs were used for training. Test and validation sets consisted of 968 and 4000 slabs, respectively. The best performing across all anomaly detectors had an area under the receiver operating characteristic of 0.99. All frameworks were shown to achieve high performance and generalize well for the different retinal diseases. Heat maps were generated to visualize the quality of the frameworks' ability to localize anomalous areas of the image. : This study shows that with the use of pre-trained feature extractors, the frameworks tested can generalize to the domain of retinal OCT scans and achieve high image-level ROC-AUC scores. The localization results of these frameworks are promising and successfully capture areas that indicate the presence of retinal pathology. Moreover, such frameworks have the potential to uncover new biomarkers that are difficult for the human eye to detect. Frameworks for anomaly detection and localization can potentially be integrated into clinical decision support and automatic screening systems that will aid ophthalmologists in patient diagnosis, follow-up, and treatment design. This work establishes a solid basis for further development of automated anomaly detection frameworks for clinical use.
PubMed: 38892804
DOI: 10.3390/jcm13113093 -
Journal of Clinical Medicine May 2024Depression has been shown to be associated with eye diseases, including dry eye disease (DED), cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic... (Review)
Review
Depression has been shown to be associated with eye diseases, including dry eye disease (DED), cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). This narrative review explores potential pathophysiological connections between depression and eye disease, as well as its potential correlations with ocular parameters. : A literature search was conducted in August 2022 in PUBMED, EMBASE, and PsycINFO. Published articles related to the subject were consolidated and classified according to respective eye diseases and pathophysiological mechanisms. : The literature reviewed suggests that common pathophysiological states like inflammation and neurodegeneration may contribute to both depression and certain eye diseases, while somatic symptoms and altered physiology, such as disruptions in circadian rhythm due to eye diseases, can also influence patients' mood states. Grounded in the shared embryological, anatomical, and physiological features between the eye and the brain, depression is also correlated to changes observed in non-invasive ophthalmological imaging modalities, such as changes in the retinal nerve fibre layer and retinal microvasculature. : There is substantial evidence of a close association between depression and eye diseases. Understanding the underlying concepts can inform further research on treatment options and monitoring of depression based on ocular parameters.
PubMed: 38892791
DOI: 10.3390/jcm13113081 -
International Journal of Molecular... May 2024Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often... (Review)
Review
Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.
Topics: Humans; Endothelial Cells; Wet Macular Degeneration; Animals; Vascular Endothelial Growth Factor A; Ranibizumab; Angiogenesis Inhibitors; Metabolic Networks and Pathways; Neovascularization, Pathologic
PubMed: 38892113
DOI: 10.3390/ijms25115926 -
International Journal of Molecular... May 2024The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along... (Review)
Review
The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.
Topics: Humans; Glymphatic System; Animals; Optic Nerve; Retina; Eye; Glaucoma
PubMed: 38891923
DOI: 10.3390/ijms25115734 -
Molecular Neurodegeneration Jun 2024Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to...
BACKGROUND
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death.
METHODS
A combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question.
RESULTS
UA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy.
CONCLUSIONS
Collectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.
Topics: Animals; Mice; Coumarins; Autophagy; Macular Degeneration; Retina; Mitophagy; Sequestosome-1 Protein; Lysosomes; Humans; Disease Models, Animal; Neuroprotective Agents; Mice, Inbred C57BL; Iodates
PubMed: 38890703
DOI: 10.1186/s13024-024-00739-3 -
Graefe's Archive For Clinical and... Jun 2024Little is known about the utilization of low vision services (LVS) in Germany. To understand which persons and how often these services would be utilized, this study...
PURPOSE
Little is known about the utilization of low vision services (LVS) in Germany. To understand which persons and how often these services would be utilized, this study aimed to investigate low vision aids (LVAs) provision in an urban setting and to describe user characteristics and trends in their characteristics.
METHODS
A retrospective study based on a population-based healthcare claims database in Cologne (N = ~ 500,000), Germany. The study population comprised individuals, who were continuously insured at four large statutory health insurers and who redeemed a prescription for visual aids or aids for blindness between January 2014 and December 2017. We examined their socio-demographic and clinical characteristics. Trends in characteristics were examined with logistic and linear regression models over time.
RESULTS
Out of ~ 500,000 persons, 781 unique individuals (~ 0.2%) redeemed an LVA prescription. They were mainly female (68.7%), 60 years or older (75.3%) and had macular degeneration (50.6%) and/or glaucoma (25.9%). In the working-age subgroup, 33.8% were employed. Visual aids were most often prescribed (74.1%) and of all types of LVAs, individuals most commonly redeemed a prescription for magnifiers (35.8%), screen readers (34.3%) and/or canes (17.1%). Of the entire study population, 75.4% received their prescription from an ophthalmologist, 5.3% from a general practitioner and 7.1% from other medical specialists. Significant trends in characteristics of individuals who redeemed an LVA prescription were not found.
CONCLUSIONS
Between 2014 and 2017, 781 individuals in Cologne redeemed an LVA prescription. They had characteristics which mostly can be explained by the epidemiology of VI. Results indicate that individuals that redeemed LVAs have a magnification requirement of ≥ 1.5-fold and ≥ 6-fold. Furthermore, next to ophthalmologists, general practitioners and other medical specialists seem to play a role in LVA provision as well, which should be taken into account by policy makers when planning interventions for increasing LVS provision. Our findings provide a starting point to examine LVS provision in Germany.
PubMed: 38888805
DOI: 10.1007/s00417-024-06541-7 -
Scientific Reports Jun 2024In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical...
In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch's Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.
Topics: Humans; Choroidal Neovascularization; Tomography, Optical Coherence; Female; Male; Retrospective Studies; Aged; Macular Degeneration; Aged, 80 and over; Image Processing, Computer-Assisted; Middle Aged; Fluorescein Angiography
PubMed: 38886462
DOI: 10.1038/s41598-024-61551-z