In vivo confocal microscopy qualitative investigation of the relationships between lattice corneal dystrophy deposition and corneal nerves.
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ABSTRACT: Background
To investigate the corneal neurotropic phenomenon in patients with lattice corneal dystrophy (LCD) with in vivo laser scanning confocal microscopy (IVCM).Methods
IVCM was performed on a total of 15 patients (28 eyes) with LCD annually at a follow-up. A collection of the data was acquired to be analyzed.Results
As indicated by the analysis, the LCD patients' normal corneal stromal nerves (Grade 0) presented a decline with the prolongation of the follow-ups, corresponding to a gradual increase in grade I and II involving amyloid-wrapped nerve fibers, which demonstrated that the growing amount of amyloid deposit due to the corneal nerve invasion increased slowly over time.Conclusions
The neurotropic phenomenon could increase with its severity in the corneal lesion of the patients with LCD, and also reflect the distribution of the corneal nerves, to some extent. IVCM provides a rapid, noninvasive way to observe the corneal nerves, which can be an efficient means of better understanding the development of LCD.
SUBMITTER: Zhu F
PROVIDER: S-EPMC8711164 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeIn vivo confocal microscopy (IVCM) is a noninvasive, reproducible, and inexpensive diagnostic tool for corneal diseases. However, widespread and effortless image acquisition in IVCM creates serious image analysis workloads on ophthalmologists, and neural networks could solve this problem quickly. We have produced a novel deep learning algorithm based on generative adversarial networks (GANs), and we compare its accuracy for automatic segmentation of subbasal nerves in IVCM images with a fully convolutional neural network (U-Net) based method.MethodsWe have collected IVCM images from 85 subjects. U-Net and GAN-based image segmentation methods were trained and tested under the supervision of three clinicians for the segmentation of corneal subbasal nerves. Nerve segmentation results for GAN and U-Net-based methods were compared with the clinicians by using Pearson's R correlation, Bland-Altman analysis, and receiver operating characteristics (ROC) statistics. Additionally, different noises were applied on IVCM images to evaluate the performances of the algorithms with noises of biomedical imaging.ResultsThe GAN-based algorithm demonstrated similar correlation and Bland-Altman analysis results with U-Net. The GAN-based method showed significantly higher accuracy compared to U-Net in ROC curves. Additionally, the performance of the U-Net deteriorated significantly with different noises, especially in speckle noise, compared to GAN.ConclusionsThis study is the first application of GAN-based algorithms on IVCM images. The GAN-based algorithms demonstrated higher accuracy than U-Net for automatic corneal nerve segmentation in IVCM images, in patient-acquired images and noise applied images. This GAN-based segmentation method can be used as a facilitating diagnostic tool in ophthalmology clinics.Translational relevanceGenerative adversarial networks are emerging deep learning models for medical image processing, which could be important clinical tools for rapid segmentation and analysis of corneal subbasal nerves in IVCM images.
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Project description:PurposeSegmentation and evaluation of in vivo confocal microscopy (IVCM) images requires manual intervention, which is time consuming, laborious, and non-reproducible. The aim of this research was to develop and validate deep learning-based methods that could automatically segment and evaluate corneal nerve fibers (CNFs) and dendritic cells (DCs) in IVCM images, thereby reducing processing time to analyze larger volumes of clinical images.MethodsCNF and DC segmentation models were developed based on U-Net and Mask R-CNN architectures, respectively; 10-fold cross-validation was used to evaluate both models. The CNF model was trained and tested using 1097 and 122 images, and the DC model was trained and tested using 679 and 75 images, respectively, at each fold. The CNF morphology, number of nerves, number of branching points, nerve length, and tortuosity were analyzed; for DCs, number, size, and immature-mature cells were analyzed. Python-based software was written for model training, testing, and automatic morphometric parameters evaluation.ResultsThe CNF model achieved on average 86.1% sensitivity and 90.1% specificity, and the DC model achieved on average 89.37% precision, 94.43% recall, and 91.83% F1 score. The interclass correlation coefficient (ICC) between manual annotation and automatic segmentation were 0.85, 0.87, 0.95, and 0.88 for CNF number, length, branching points, and tortuosity, respectively, and the ICC for DC number and size were 0.95 and 0.92, respectively.ConclusionsOur proposed methods demonstrated reliable consistency between manual annotation and automatic segmentation of CNF and DC with rapid speed. The results showed that these approaches have the potential to be implemented into clinical practice in IVCM images.Translational relevanceThe deep learning-based automatic segmentation and quantification algorithm significantly increases the efficiency of evaluating IVCM images, thereby supporting and potentially improving the diagnosis and treatment of ocular surface disease associated with corneal nerves and dendritic cells.
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Project description:PurposeSpecific components of transforming growth factor-beta-induced protein (TGFBIp) responsible for amyloid deposits in lattice corneal dystrophy (LCD) have not been delineated. LCD has been associated with various TGFBIp mutations such as R124C, L518P, and L527R. Using recombinant TGFBIp, this study was undertaken to identify TGFBIp components potentially contributing to the protein deposits in LCD.MethodsRecombinant wild-type (WT) TGFBIp and four mutants (R124C, R124H, L518P, and L527R) were generated in HEK293FT cells. WT and mutant TGFBIp were collected from crude cell lysates or purified from culture media. Immunoblot analyses were performed with four different anti-TGFBIp antibodies raised against various regions of TGFBIp.ResultsConsistent with the authors' previous findings, purified recombinant proteins are more prone to polymerize than crude cell lysates. As expected, all monomers and polymers of TGFBIp WT and mutants were detected by these antibodies. However, the authors noted WT and TGFBIp mutants showed differential reactivities with these antibodies. A 47-kDa band was detected in purified 2-tag proteins of L518P by all four antibodies. A unique 43-kDa band was detected in both 1-tag cell lysates and purified proteins of R124C by the authors' custom-made antibody (KE50) and a commercial anti-TGFBIp.ConclusionsBased on its universal reactivity with various antibodies, the authors surmise that the 47-kDa protein is a ubiquitous TGFBIp fragment derived from the N-terminus of the L518P mutant. The fact that the 43-kDa protein fragment was present primarily in R124C and R124H but not in WT implicates its potential role in the protein deposits of LCD.
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Project description:BackgroundPre-Descemet corneal dystrophy (PDCD) is characterized by the presence of numerous, tiny, polymorphic opacities immediately anterior to Descemet membrane, which is a rare form of corneal stromal dystrophy and hard to be diagnosed. In vivo confocal microscopy (IVCM) is a useful tool to examine the minimal lesions of the cornea at the cellular level. In this article, we report a rare case of PDCD associated with X-linked ichthyosis and evaluate IVCM findings.Case presentationWe present a 34-year-old male Chinese patient with PDCD associated with X-linked ichthyosis. Slit-lamp biomicroscopy showed the presence of tiny and pleomorphic opacities in the posterior stroma immediately anterior to Descemet membrane bilaterally. IVCM revealed regular distributed hyperreflective particles inside the enlarged and activated keratocytes in the posterior stroma. Hyperreflective particles were also observed dispersedly outside the keratocytes in the anterior stroma. Dermatological examination revealed that the skin over the patient's entire body was dry and coarse, with thickening and scaling of the skin in the extensor side of the extremities. PCR results demonstrated that all ten exons and part flanking sequences of STS gene failed to produce any amplicons in the patient.ConclusionsIVCM is useful for analyzing the living corneal structural changes in rare corneal dystrophies. We first reported the IVCM characteristics of PDCD associated with X-linked ichthyosis, which was caused by a deletion of the steroid sulfatase (STS) gene, confirmed by gene analysis.
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Project description:TGFBI associated Corneal Dystrophies (CD) are a group of inherited protein folding disorders linked to the mutation in the TGFBI gene. The resultant mutant protein (TGFBIp) is deposited as insoluble protein aggregates in various layers of the cornea leading to corneal opacity and poor vision. Depending on the type of mutation the deposits may be classified as amyloid fibrillar type, amorphous globular aggregates or a mixed form of both fibrils and amorphous aggregates. However, the molecular mechanism of the mutant-induced amyloidosis is not fully understood. This study aimsto characterize truncated peptides enriched in the amyloid aggregates and to identify the protein composition of the corneal aggregates derived from dystrophic patients using LC-MS/MS and compare the data with normal control cornea. We have identified several amyloid associated proteins, non-fibrillar amyloid associated proteins and TGFBIp as the major component of the corneal deposits. The results suggest that Apolipoprotein A-IV, Apolipoprotein E and Serine protease HtrA1 to be significantly enriched in the corneal deposits compared to the normal cornea. Comparative analysis of peptides from corneal deposits of patient and control identified several peptides of TGFBIp which are enriched in patient tissue and may form the core of corneal amyloids. Most of the peptides represent the 4th FAS-1 domain of the protein. Biophysical studies of two such peptides (G515DNRFSMLVAAIQSAGLTETLNR533 and Y571HIGDEILVSGGIGALVR588) demonstrate that they readily form amyloid fibrils under physiological conditions, confirming their intrinsic propensity to form amyloid fibrils. The identification of proteins which are involved in other protein misfolding disorders as well as identification of peptides from TGFBIp which form -amyloid core highlight that the mechanism of amyloid formation may share common molecular pathways.
2022-02-28 | PXD006640 | Pride
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Project description:PurposeTo evaluate corneal nerve and immune cell alterations in Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation and endothelial cell loss.DesignProspective, cross-sectional, controlled study.MethodsThirty-three eyes with FECD were compared to 13 eyes with PBK and 17 normal age-matched control eyes at a tertiary referral center. FECD was classified into early (without edema) and late stage (with edema). Corneal IVCM and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC) alterations were evaluated and correlated to clinical parameters.ResultsFECD and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5 ± 1.3 and 2.9 ± 0.7 mm/mm2) and number (8.8 ± 1.1 and 2.2 ± 0.4 n/frame), compared to controls (23.3 ± 8.1 mm/mm2 and 25.9 ± 1.3 n/frame). Decreased nerves corresponded to diminished sensation in FECD (4.9 ± 0.2 cm; R = 0.32; P = .045), compared to controls (5.9 ± 0.04 cm). Early- and late-stage FECD showed significantly reduced total nerve length (13.1 ± 1.4 and 9.9 ± 1.2 mm/mm2, respectively) and number (8.2 ± 2.5 and 6.5 ± 2.1 n/frame), compared to controls (P < .001). DC density was significantly increased in FECD (57.8 ± 10.4 cells/mm2; P = .01), but not in PBK (47.7 ± 11.6 cells/mm2; P = .60) compared to controls (22.5 ± 4.5 cells/mm2). A subset of early FECD patients (7/22) demonstrated very high DC density (>100/mm2).ConclusionIVCM demonstrates profound diminishment of subbasal corneal nerves in early- and late-stage FECD and in PBK, correlating to decreased sensation. Increased DC density in early FECD demonstrates potential subclinical inflammation. The data suggest that reduction in subbasal nerves and increased immune activation may play a role in the pathophysiology of FECD.
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Project description:Background: The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. Methods: CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length (CNFL), corneal nerve fiber width, corneal nerve fiber area, and dendritic cell and non-dendritic cell density with or without nerve fiber contact were quantified. Results: Patients with TN had significantly lower CNFD and CNFL but no difference for any other corneal nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in corneal nerve and cell parameters between patients with TN with and without involvement of the ophthalmic nerve (V1) or with nerve vessel conflict. Conclusion: Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical corneal nerve loss in patients with TN.
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