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Book ; Online: Confocal Laser Microscopy

Lagali, Neil

Principles and Applications in Medicine, Biology, and the Food Sciences

2013

Keywords	Microscopy ; Industrial applications of scientific research & technological innovation
Language	English
Size	1 electronic resource (246 pages)
Publisher	IntechOpen
Document type	Book ; Online
Note	English
HBZ-ID	HT030645673
ISBN	9789535142522 ; 9535142526
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: The Inferocentral Whorl Region and its Directional Patterns in the Corneal Sub-Basal Nerve Plexus: A review.

Badian, Reza A / Lagali, Neil

Experimental eye research

2024 , Page(s) 109926

Abstract: There has been a growing application of in vivo confocal microscopy (IVCM) in the examination of corneal microstructure, including different corneal layers and corneal nerve fibers in health and in pathological conditions. Corneal nerves forming the sub- ... ...

Abstract	There has been a growing application of in vivo confocal microscopy (IVCM) in the examination of corneal microstructure, including different corneal layers and corneal nerve fibers in health and in pathological conditions. Corneal nerves forming the sub-basal nerve plexus (SBNP) beneath the corneal basal epithelial cell layer in particular have been intensively researched in health and disease as a marker for corneal neurophysioanatomical and degenerative changes. One intriguing feature in the SBNP that is found inferior to the corneal apex, is a whorl-like pattern (or vortex) of nerves, which represents an anatomical landmark. Evidence has indicated that the architecture of this 'whorl region' is dynamic, changing with time in healthy individuals but also in disease conditions such as in diabetic neuropathy and keratoconus. This review summarizes the known information regarding the characteristics and significance of the whorl region of nerves in the corneal SBNP, as a potential area of high relevance for future disease monitoring and diagnostics.
Language	English
Publishing date	2024-05-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2024.109926
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Article ; Online: Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential.

Lagali, Neil

Current eye research

2019 Volume 45, Issue 3, Page(s) 278–290

Abstract: The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of ... ...

Abstract	The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or re-cellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed.
MeSH term(s)	Animals ; Corneal Diseases/pathology ; Corneal Diseases/physiopathology ; Corneal Diseases/surgery ; Corneal Stroma/pathology ; Corneal Stroma/physiopathology ; Corneal Transplantation/methods ; Humans ; Regeneration/physiology ; Stem Cell Transplantation/methods ; Tissue Engineering/methods
Language	English
Publishing date	2019-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2019.1663874
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Article ; Online: Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population.

Al-Hawasi, Abbas / Lagali, Neil

BMC ophthalmology

2022 Volume 22, Issue 1, Page(s) 278

Abstract: Background: The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can ... ...

Abstract	Background: The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. Methods: A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. Results: One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 ± 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P > 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 ± 0.07 mm Conclusion: Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.
MeSH term(s)	Cross-Sectional Studies ; Female ; Humans ; Male ; Nerve Fibers/pathology ; Prospective Studies ; Retinal Ganglion Cells/pathology ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2022-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2050436-6
ISSN	1471-2415 ; 1471-2415
ISSN (online)	1471-2415
ISSN	1471-2415
DOI	10.1186/s12886-022-02488-7
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Article ; Online: MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges.

Moustardas, Petros / Aberdam, Daniel / Lagali, Neil

Cells

2023 Volume 12, Issue 4

Abstract: Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate ...

Abstract	Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.
MeSH term(s)	Mitogen-Activated Protein Kinases/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; Phosphorylation ; MAP Kinase Signaling System/physiology
Chemical Substances	Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12040617
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Article ; Online: Methods for evaluation of corneal nerve fibres in diabetes mellitus by in vivo confocal microscopy: a scoping review protocol.

Sandvik, Siv Aaseth / Sundling, Vibeke / Lagali, Neil

BMJ open

2023 Volume 13, Issue 4, Page(s) e070017

Abstract: Introduction: Globally, 422 million people have diabetes. Late complications of diabetes are blindness, kidney failure, heart attack, stroke and lower limb amputation. The prevalence of diabetic peripheral neuropathy and diabetic retinopathy is 50% and ... ...

Abstract	Introduction: Globally, 422 million people have diabetes. Late complications of diabetes are blindness, kidney failure, heart attack, stroke and lower limb amputation. The prevalence of diabetic peripheral neuropathy and diabetic retinopathy is 50% and 35%, respectively. In vivo confocal microscopy (IVCM) is a rapid, non-invasive method to evaluate subbasal corneal nerve fibres, which are small fibres of the peripheral nervous system. Corneal nerve fibre changes can be a marker of diabetic peripheral neuropathy. There is currently no gold-standard procedure for IVCM imaging, image processing or quantitative analysis of the corneal nerve fibres in the subbasal plexus. This protocol describes a scoping review to map, summarise and critically evaluate current methods used with IVCM evaluation in people with diabetes mellitus. Methods: The scoping review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping review. A comprehensive search of the literature will be conducted in MEDLINE, Embase, Cochrane, Scopus and Web of Science. The search strategy will include terms related to IVCM, diabetes and corneal nerve fibres. We will set inclusion and exclusion criteria prior to the search, and two reviewers will screen titles and abstracts independently. One reviewer will full text read eligible articles and chart data from the studies. A descriptive summary of the methods used in imaging, image processing and quantitative analysis of peripheral corneal nerve fibres by IVCM will be written. Ethics and dissemination: Ethical approval is not required since this is a scoping review based on previously published articles. The findings will be published in a scientific peer-reviewed journal.
MeSH term(s)	Humans ; Diabetic Neuropathies/diagnostic imaging ; Cornea/diagnostic imaging ; Cornea/innervation ; Research Design ; Nerve Fibers ; Microscopy, Confocal/methods ; Diabetes Mellitus ; Systematic Reviews as Topic ; Review Literature as Topic
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-070017
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Article: Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis.

Al-Hawasi, Abbas / Lagali, Neil / Fagerholm, Per / Huang-Link, Yumin

Journal of clinical medicine

2023 Volume 12, Issue 6

Abstract: A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use ... ...

Abstract	A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12062240
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Article ; Online: Femtosecond Laser-Assisted Surgery for Implantation of Bioengineered Corneal Stroma to Promote Corneal Regeneration.

Lagali, Neil / Rafat, Mehrdad

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2145, Page(s) 197–214

Abstract: The femtosecond laser has achieved widespread use in ophthalmology owing to its ability to deliver focused high energy that is rapidly dissipated and thereby does not damage surrounding tissue outside the precise focal region. Extremely accurate and ... ...

Abstract	The femtosecond laser has achieved widespread use in ophthalmology owing to its ability to deliver focused high energy that is rapidly dissipated and thereby does not damage surrounding tissue outside the precise focal region. Extremely accurate and smooth cuts can be made by the laser, enabling a range of applications in anterior segment surgery. Minimally invasive corneal surgical procedures can be performed using the femtosecond laser, and here we describe the application of such procedures to improve implantation of bioengineered materials into the cornea. Bioengineered corneal tissue, including the collagenous corneal stroma, promises to provide a virtually unlimited supply of biocompatible tissue for treating multiple causes of corneal blindness globally, thereby circumventing problems of donor tissue shortages and access to tissue banking infrastructure. Optimal implantation of bioengineered materials, however, is required, in order to facilitate postoperative wound healing for the maintenance of corneal transparency and avoidance of postoperative complications such as scarring, inflammation, and neovascularization. Moreover, the avoidance of a detrimental physiological physiological wound healing response is critical for facilitating the corneal stromal regeneration enabled by the bioengineered stroma. Without proper implantation, the tissue response will favor inflammation and pathologic processes instead of quiescent keratocyte migration and new collagen production. Here we describe several procedures for optimized biomaterial implantation into the corneal stroma, that facilitate rapid wound healing and regenerative restoration of corneal transparency without the use of human donor tissue. A step-by-step methodology is provided for the use of the femtosecond laser and associated techniques, to enable seamless integration of bioengineered materials into the corneal stroma.
MeSH term(s)	Bioengineering/methods ; Cornea/growth & development ; Cornea/pathology ; Corneal Stroma/growth & development ; Corneal Stroma/pathology ; Corneal Stroma/transplantation ; Humans ; Laser Therapy ; Regeneration/genetics
Language	English
Publishing date	2020-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0599-8_14
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Article ; Online: AI-Based Decision-Support System for Diagnosing Acanthamoeba Keratitis Using In Vivo Confocal Microscopy Images.

Lincke, Alisa / Roth, Jenny / Macedo, António Filipe / Bergman, Patrick / Löwe, Welf / Lagali, Neil S

Translational vision science & technology

2023 Volume 12, Issue 11, Page(s) 29

Abstract: Purpose: In vivo confocal microscopy (IVCM) of the cornea is a valuable tool for clinical assessment of the cornea but does not provide stand-alone diagnostic support. The aim of this work was to develop an artificial intelligence (AI)-based decision- ... ...

Abstract	Purpose: In vivo confocal microscopy (IVCM) of the cornea is a valuable tool for clinical assessment of the cornea but does not provide stand-alone diagnostic support. The aim of this work was to develop an artificial intelligence (AI)-based decision-support system (DSS) for automated diagnosis of Acanthamoeba keratitis (AK) using IVCM images. Methods: The automated workflow for the AI-based DSS was defined and implemented using deep learning models, image processing techniques, rule-based decisions, and valuable input from domain experts. The models were evaluated with 5-fold-cross validation on a dataset of 85 patients (47,734 IVCM images from healthy, AK, and other disease cases) collected at a single eye clinic in Sweden. The developed DSS was validated on an additional 26 patients (21,236 images). Results: Overall, the DSS uses as input raw unprocessed IVCM image data, successfully separates artefacts from true images (93% accuracy), then classifies the remaining images by their corneal layer (90% accuracy). The DSS subsequently predicts if the cornea is healthy or diseased (95% model accuracy). In disease cases, the DSS detects images with AK signs with 84% accuracy, and further localizes the regions of diagnostic value with 76.5% accuracy. Conclusions: The proposed AI-based DSS can automatically and accurately preprocess IVCM images (separating artefacts and sorting images into corneal layers) which decreases screening time. The accuracy of AK detection using raw IVCM images must be further explored and improved. Translational relevance: The proposed automated DSS for experienced specialists assists in diagnosing AK using IVCM images.
MeSH term(s)	Humans ; Acanthamoeba Keratitis/diagnosis ; Artificial Intelligence ; Cornea/diagnostic imaging ; Microscopy, Confocal/methods ; Research Design
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2674602-5
ISSN	2164-2591 ; 2164-2591
ISSN (online)	2164-2591
ISSN	2164-2591
DOI	10.1167/tvst.12.11.29
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Article ; Online: Relapse of pathological angiogenesis: functional role of the basement membrane and potential treatment strategies.

Mukwaya, Anthony / Jensen, Lasse / Lagali, Neil

Experimental & molecular medicine

2021 Volume 53, Issue 2, Page(s) 189–201

Abstract: Blinding eye diseases such as corneal neovascularization, proliferative diabetic retinopathy, and age-related macular degeneration are driven by pathological angiogenesis. In cancer, angiogenesis is key for tumor growth and metastasis. Current ... ...

Abstract	Blinding eye diseases such as corneal neovascularization, proliferative diabetic retinopathy, and age-related macular degeneration are driven by pathological angiogenesis. In cancer, angiogenesis is key for tumor growth and metastasis. Current antiangiogenic treatments applied clinically interfere with the VEGF signaling pathway-the main angiogenic pathway-to inhibit angiogenesis. These treatments are, however, only partially effective in regressing new pathologic vessels, and the disease relapses following cessation of treatment. Moreover, the relapse of pathological angiogenesis can be rapid, aggressive and more difficult to treat than angiogenesis in the initial phase. The manner in which relapse occurs is poorly understood; however, recent studies have begun to shed light on the mechanisms underlying the revascularization process. Hypotheses have been generated to explain the rapid angiogenic relapse and increased resistance of relapsed disease to treatment. In this context, the present review summarizes knowledge of the various mechanisms of disease relapse gained from different experimental models of pathological angiogenesis. In addition, the basement membrane-a remnant of regressed vessels-is examined in detail to discuss its potential role in disease relapse. Finally, approaches for gaining a better understanding of the relapse process are discussed, including prospects for the management of relapse in the context of disease.
MeSH term(s)	Animals ; Basement Membrane/metabolism ; Basement Membrane/pathology ; Biomarkers ; Collagen/genetics ; Collagen/metabolism ; Disease Management ; Disease Susceptibility ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; Humans ; Neovascularization, Pathologic/etiology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/therapy ; Recurrence ; Signal Transduction
Chemical Substances	Biomarkers ; Collagen (9007-34-5)
Language	English
Publishing date	2021-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-021-00566-2
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